The Panacea

PaThneacea
VOLUME 1, 2021 (INAUGURAL ISSUE)



Contents 4
5
Message from the Dean 6
Message from the Editor-in-Chief 7
Foreword for Inaugural Issue of The Panacea 8
Editorial Board 11
History of Faculty of Pharmacy Universiti Malaya 14
Congratulatory Note from Student Society and Alumni 20
Staff of the Faculty of Pharmacy 2020/2021 21
Summary of 2020 Main Faculty of Pharmacy Activities/ Events
Highlights of the Faculty’s Research 21
Complementary and Alternative Medicine Use in Patients with
Chronic Kidney Disease: What is our Concern? 25
Virtual Screening of Potential Tripeptide Inhibitors Towards 26
Ns3 Serine Protease of Dengue Virus
The Future of Nanotherapeutics in Anti-Cancer Drug Delivery 29
Reprocess and Repurpose of Active Pharmaceutical Ingredients 33
(Apis) from Expired Pharmaceutical Products (Epps) - 34
An Eco-Friendly Approach- Mini Review 36
Past Activities 40
Awards & Rewards
Technical Services @ Pharmacy of Faculty
Contact Us

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Message from the Dean Prof. Dr. Hasniza
Zaman Huri
Welcome to the first edition of The Panacea, Dean
our Faculty of Pharmacy bulletin. This first Faculty of Pharmacy
publication of The Panacea marks another Universiti Malaya
breakthrough for the Faculty of Pharmacy Universiti
Malaya.

We have been celebrating many milestones
since we started operating as the newest Faculty in
Universiti Malaya in 2019. Our journey started as the
Department of Pharmacy, established as a department
under the Faculty of Medicine back in 1995. This
faculty was fully operational in September 2019,
with the appointment of the dean and our two deputy
deans on 1st September 2019. While our faculty
status is recent, we bring more than two decades of
achievements and experience from our existence as
the Department of Pharmacy. Since our beginnings
as the Department of Pharmacy up until now, there
have been more than 21 batches of students who have
graduated from our Bachelor of Pharmacy (Honours)
degree program, which have produced more than
1200 pharmacists and with hundreds of students
pursued their postgraduate degrees with us.

Over the years, we have charted a journey
that centred on excellence, progress, and growth,
culminating in the current achievement of our highest
ranking to date at #97 by the QS Global World Ranking
for Pharmacology and Pharmacy. As we move forward,
we hope to continue our tradition of excellence and
positively impact the community around us.

Lastly, my heartiest congratulations to the editorial
committee of The Panacea and thank you for the hard
work in making this bulletin a reality. This inaugural
edition of The Panacea reflects the aspirations of the
faculty to contribute to the betterment of society. We
hope that our bulletin will benefit our professional
colleagues as well as the wider society.

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Message from the Editor-in-Chief Rozana Othman
Editor-in-Chief
Congratulations to the Faculty of Pharmacy The Panacea
Universiti Malaya for this first edition of the
faculty’s bulletin, The Panacea. Panacea means a THE PANACEA
remedy that can cure ailments or solution to problems
and difficulties. This name is fitting in the midst of the
global challenges facing us during this COVID-19
pandemic. The Panacea is published 1 issue a year.

The establishment of the Faculty of Pharmacy
Universiti Malaya in 2019 as the thirteenth faculty in
our university makes the Faculty of Pharmacy amongst
the youngest faculties in Universiti Malaya. I hope the
current achievement of this faculty, with its highest
ranking to date at #97 by the QS Global World Ranking
for Pharmacology and Pharmacy, will be the beginning
of more notable achievements in its future. This faculty
has come a long way from its humble beginnings as
the Department of Pharmacy more than two decades
ago. Its history of growth, progress and achievements
as the Department of Pharmacy under the umbrella
of the Faculty of Medicine from 1995 to 2019 has led
to its current accomplishments with more successful
endeavours expected in its bright future.

Presently, Universiti Malaya is undergoing
change and growth, requiring reassessments and
improvements, as well as reorientation of our values
and our direction. As a new faculty, I anticipate that
the Faculty of Pharmacy will continue to contribute
alongside the other faculties, academies, institutes
and centres of Universiti Malaya towards realising the
vision and achieving the mission of Universiti Malaya.

It is my hope that Panacea will be a tribute to
the core values of Universiti Malaya, which reflect
the mission, purpose, philosophy, and beliefs of our
campus community. This bulletin will reflect the
qualities of Passion, Oneness, Integrity, Sincerity and
Empathy that we want to foster and nurture in the
Universiti Malaya community as we work towards our
vision to be A Global University Impacting The World.

The aspiration of The Panacea is aligned with
the mission of Universiti Malaya, where we aspire in
Pushing The Boundaries Of Knowledge And Nurturing
Aspiring Leaders. I hope The Panacea will be a
beneficial resource to the campus community as well
as to the society at large.

5

Foreword for Inaugural Issue of
The Panacea

Pharmaceutical development worldwide is Syed Mahmood
remarkable and reaches every individual across Editorial Coordinator
the globe. The effort made by pharmaceutical The Panacea
industries, academia, and social pharmacy
practitioners (hospital and community pharmacist)
results in consistently high-quality products and
information, thus improving the quality of life. To
maintain and improve these standards, many institutes
such as USFDA, NPRA, and WHO, provide updated
knowledge on various issues related to pharmaceutical
drugs and their use. Academia plays a significant
role in enlightening the industry and making this
knowledge a reality on the ground.

Panacea’s mission is to provide a platform and
avenue for academia to publish their research updates
and ideas and disseminate innovative thoughts on
pharmaceutical, life sciences, and healthcare-related
issues. Research papers give a genuine insight into
specific areas by using real-world examples to report
significant developments, describing the relevant
theoretical background with a workable algorithm.

Panacea is the first magazine from the Faculty
of Pharmacy Universiti Malaya that aims to publish
industry updates and activities throughout the year.
The first issue covers 2020 happenings, and we aim to
publish two issues per volume in upcoming years. The
information will be categorised as follows:

• Research papers
• Review articles
• Abstracts
• Expert opinions, and
• Social and educational activities.

The Faculty of Pharmacy Universiti Malaya hopes
this initiative will give readers a better understanding
of what is happening in the industry and enhance
the quality of learning. We welcome enquiries and
feedback on this issue and potential publications in
future issues.

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Editorial Board

Advisors
Prof. Dr. Hasniza Zaman Huri, Dean
Assoc. Prof. Dr. Najihah Mohd Hashim, Deputy Dean (Academic)
Prof. Dr. Chung Lip Yong, Honorary Professor

Editorial In Chief
Assoc. Prof. Dr. Rozana Othman
Deputy Dean (Research & Development)

Editorial Coordinator
Dr. Syed Mahmood

Editor Editor Editor
Dr. Zarif Mohamed Dr. Phan Chia Wei Dr. Fatiha Hana

Sofian Shabaruddin

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Going back in history, the second Bachelor of Pharmacy programme in
Malaysia was established under the Faculty of Medicine on 1st March
1995, driven by the need of the country to train more pharmacists for the
healthcare sector and healthcare-related industry. At the time of its establishment,
there were only seven academic staff members; Prof. Yeoh Peng Nam, who was the
first Head of Department, the late Prof. William Marlow, Dr. Rajan Radhakrishnan,
Dr. Chung Lip Yong, Dr. Chua Siew Siang, the late Assoc. Prof. Syafiq Abdullah
and the late Assoc. Prof. Hadida Hashim. Lecturers from other departments within
the Faculty of Medicine and the Faculty of Science also contributed their teaching
manpower for the programme. The administrative office back then was located
at the Department of Pharmacology, Faculty of Medicine while the offices for
academic staff were mainly located at the present location for the Department of
Nursing. Teaching facilities were within the same location while practical classes
were conducted at MD1 and MD2, Faculty of Medicine.

History of FUanciuvletrysiotfi MPhaalramyaacy

Prof. Dr. Yeoh Peng Nam On 26 June 1995, the Department of Pharmacy
The First Head of opened its doors to the first batch of thirty-six
Department of Pharmacy students. The first-year students were introduced
Universiti Malaya to basic sciences including physiology, anatomy,
biochemistry, drug literacy, general, physical and
organic chemistry. Then in their second-year, the
students took on pharmacopoeias, purity and official
standards, quantitative analysis, medicinal chemistry,
pharmaceutical technology, pharmacology and
clinical pharmacy. In their third-year, students were
exposed to more clinical pharmacy and industrial
pharmacy modules. Students were also required to
conduct original research, produced a dissertation
and present their findings before graduation. The
first batch students completed their studies within
three and a half years. The duration of study for
subsequent batches was increased to four years due to
introduction of additional university courses under the
semester system. The second intake welcomed forty
students and the number for each intake increased to
seventy to eighty students in subsequent years. The
Department of Pharmacy produced 1200 pharmacy
graduates between 1995 and 2019.

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Pioneering batch 1995; Front row (from left): Dr. Rajan Radhakrishnan, Dr. Chung Lip Yong, Prof. Dr.
Annuar Zaini (Dean of Faculty of Medicine), Prof. Dr. Yeoh Peng Nam (Founding Head), the late Prof.
William Marlow, Mr. Athouan Nathan (Medical Laboratory Technologist)

In 1999, two floors of a new four-story building were officially opened to
accommodate the Department’s growing activities. In 2001, the Department
started to provide postgraduate training in Masters in Medical Sciences by
research and the Doctor of Philosophy programmes. The interest and enthusiasm
in postgraduate education continued to flourish. Up to 2019, the Department
have had more than 80 Masters in Medical Sciences graduates and PhDs.

On 1st September 2019,
the Faculty of Pharmacy was
officially announced and
was the newest Faculty in the
Universiti Malaya. The first
Dean of Faculty of Pharmacy
Universiti Malaya is Prof. Dr.
Hasniza Zaman Huri with
Assoc. Prof. Dr. Najihah
appointed as the Deputy Dean
(Academic) and Assoc. Prof.
Dr. Rozana Othman appointed
as the Deputy Dean (Research
and Development). The Faculty of Pharmacy comprises four main teaching
departments, which are: Department of Pharmaceutical Chemistry, Department
of Pharmaceutical Technology, Department of Life Sciences and Department of
Clinical Pharmacy and Pharmacy Practice.

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The newly established Faculty of Pharmacy Universiti Malaya is expected
fulfil the function of a full academic centre. The management recognized the
need to upgrade and expand the undergraduate pharmacy curriculum, teaching
and research facilities in line with the five-year strategic plan 2020-2025. The
new 4-year pharmacy undergraduate curriculum was recently approved, with
the introduction of two new masters level postgraduate courses (Masters in Drug
Discovery and Masters in Quality Assurance).

Currently, the Faculty of Pharmacy Universiti Malaya is expanding its
activities in undergraduate and postgraduate teaching, research and training,
student mobility programmes, national and international networking. Facilities
are also being upgraded or in planning. These include the Faculty of Pharmacy
Cube, which is equipped with multimedia facilities, teaching and learning rooms,
bedside teaching facilities, teaching and research equipment and others.

The Heads of Department of Pharmacy/ Dean of Faculty of
Pharmacy Universiti Malaya since its inception in 1995.

PROF. DR. YEOH THE LATE ASSOC. PROF. DR. SAMSINAH PROF. DR. CHUNG
PENG NAM PROF. DR. HADIDA HUSSAIN LIP YONG
(1995-1997) (2004-2006)
HASHIM (2001-2004, 2006)
(1997-2001)

ASSOC. PROF. DR. PROF. DR. ZORIAH PROF. DR. HASNIZA
MOHAMED IBRAHIM AZIZ ZAMAN HURI
(2019-PRESENT)
NOORDIN (2014-2019)
(2006-2014)

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Congratulatory Note from
Student Society and Alumni

CONGRATULATIONS to our Faculty of Pharmacy Mr. Abdul Muhaimin
for taking a huge step in initiating a faculty Mohamad Amin
bulletin, The Panacea. The undergraduates President, UM PharmSoc
highly appreciate and anticipate this platform to get (2020/2021)
updates and news from the faculty thus bringing the
society closer to the faculty.

We would like to take this opportunity to introduce
Pharmacy Society Universiti Malaya (UM PharmSoc),
the undergraduates’ student body of Faculty of
Pharmacy. UM PharmSoc was established in 1998
as the undergraduates recognized the importance of
having a voice to represent pharmacy undergraduates
and the need for a platform for undergraduates to be
involved in activities beyond daily lectures scheduled.

Our UM PharmSoc members put in a tremendous
effort to build a coherent relationship among pharmacy
undergraduates from different academic sessions as
we realize that an organization is weak if its members
are not united. We provide various platforms for the
students to develop soft skills in organising events
that is important for as a future pharmacist. We also
become the bridge between Malaysian Pharmacy
Students’ Association (MyPSA), a national pharmacy
student association and the students in relaying
information regarding national events and activities
held by MyPSA.

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The Faculty of Pharmacy, Postgraduate Society Mdm Thee Khim Boon
would like to congratulate the faculty for President, Postgraduate
achieving another milestone in publishing The Society, UM (2020/2021)
Panacea, a collective effort to publish academic news,
activities, scientific updates, and many more events
from the faculty to connect graduate, undergraduates,
management staffs and all the stakeholders.

The Postgraduate Society of The Faculty of
Pharmacy aims to encourage active engagement in
various advanced scientific research by supporting
and recognising outstanding achievements. The
newly formed society value every member’s effort
and support to achieve our aim. We are working
towards the registration of the society at the University
of Malaya. This year, the society will continue to
provide the opportunity to present and discuss various
research matters in Research café monthly during the
pandemic. An E-symposium is currently in our pipeline
to offer visibility of the researches conducted by the
postgraduates.

It always seems impossible until it is done.
First and foremost, as a representative of the UM
Pharmacy Alumni Organisation, I would like to
properly and formally extend our big congratulations
to the management from the Faculty of Pharmacy to
transform the previously small and humble department
into the big name it is today.

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We as alumni cannot stop from being Mr. Mohamad Adam
overwhelmed and jubilant over the news Mohamad Saladri
and hope it will continue to grow more with Vice Secretary of the
every single step taken forwards. Another appreciations UM Pharmacy Alumni
and congratulations go to the editorial members of the Organisation
newly form bulletin team, The Panacea for putting up
and publishing our first ever bulletin for the faculty.

The Panacea embodies effort, passion, and joy
across the faculty members, especially from our
lecturers. We hope that this bulletin will be a new
source of information that not only the students
and lecturers will look up to, but also for us fellow
alumni in learning new updates on the projects and
discoveries made in the faculty.

In light of this opportunity, I would like to bring
forth this organisation that is close to my heart, the UM
Pharmacy Alumni Organisation into understanding
the main reason of its establishment back in the 2019.
Our main purpose is to be the pillar of trust and
support for the faculty with any means necessary that
is required to make a great and outstanding faculty
nationally, and hopefully internationally too. Our
next purpose is to be a centre that provides tutoring,
coaching, and guidance for our alumni in enrolling
various task forces in the pharmacy industry so that
our employability rate as UM Pharmacy graduates is
100%.

We hope that with the unition of our knowledge,
passions, experiences, and networks in the organisation
will provide assistance for the faculty in handling and
managing projects in various level. In addition, we
sincerely hope that we will be able to guide our young
students in becoming a great pharmacy graduates with
a mind prepared to embark the working world. Our
AGM will be conducted soon and we look forward to
many new and exciting projects along the road with a
collaboration from the faculty.

Alone we can do so little, together we can do so
much. In unity, we stand together.

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Staff of the Faculty of Pharmacy 2020/2021

FoP Academic Staff FoP Administrative and
Supporting Staff
1 Prof. Dr. Hasniza Zaman Huri
2 Assoc. Prof. Dr. Najihah Mohd 1 Mr. Khairul Nizam Roslan
2 Madam Ernie Gireen Abdullah
Hashim 3 Mr. Abdul Aziz Ismail
3 Assoc. Prof. Dr. Rozana Othman 4 Madam Nor Nadia Alies
4 Assoc. Prof. Dr. Baharudin Ibrahim 5 Mr. Abdul Rafique Abd Jalal
5 Prof. Dr. Chung Lip Yong 6 Madam Rustini Karim
6 Dr. Amira Hajirah Abd Jamil 7 Madam Siti Aisah Basari
7 Dr. Bontha Venkata Subrahmanya 8 Ms. Salmizawati Salim
9 Madam Nurul Husna Osman
Lokesh 10 Ms. Nurul Izzati Abdul Wahab
8 Dr. Chin Sek Peng 11 Ms. Noor Akma Kamaruddin
9 Dr. Fatiha Hana Shabaruddin 12 Mr. Mohd Shazly Mohd Royani
10 Dr. Heh Choon Han 13 Mr. Mohd Asni Mohamed
11 Dr. Izyan A. Wahab 14 Mr. Mohd Najib Baharom
12 Ms. Mary Lee Hong Gee 15 Madam Mariah Ahmad Kairi
13 Dr. Kayatri Govindaraju 16 Ms. Masitah Harun
14 Dr. Leong Kok Hoong 17 Ms. Siti Nur Ezaty Mazlan
15 Madam Noorasyikin Shamsuddin 18 Madam Syamira Azwin Safarudin
16 Dr. Nur Akmarina Mohd Said 19 Madam Suhaila Nordin
17 Dr. Nusaibah Abdul Rahim 20 Mr. Norfahmi Izzuddin Ramli
18 Dr. Phan Chia Wei 21 Madam Gangeswary Sukumaran
19 Dr. Riyanto Teguh Widodo 22 Mr. Anuar Abdullah
20 Dr. Shaik Nyamathulla 23 Mr. Mohd Jauzi Mohd Shahidin
21 Dr. Sim Maw Shin
22 Dr. Syed Mahmood
23 Madam Syireen Alwi
24 Dr. Zarif Mohamed Sofian

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Prof. Dr. Hasniza Zaman Huri

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Prof. Dr. Hasniza
Zaman Huri

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Summary of 2020 Main Faculty of Pharmacy
Activities/ Events

No. Activity/ Event Date

1 Visit from External Assessor, Prof. Nick Shaw 13-16/01/2020

2 Visit from Airlangga University, Surabaya (UNAIR), 06/02/2020
Indonesia as Partner University

3 Training on information skill at the UM Library for PG 05/03/2020
students

4 Three-minute thesis (3MT) competition for PG students 12/03/2020

5 Meeting with Kyushu University as Partner University 24/07/2020

6 Visit from Malaysian Vaccines and Pharmaceuticals Sdn Bhd 20/07/2020

7 Curriculum Meeting (Mesyuarat JK Kurikulum Fakulti 28/07/2020
Bil.2/2020 Fakulti Farmasi)

8 FTIR Training by PerkinElmer Inc. 13/08/2020

9 Strategic Planning Workshop for Accreditation 24/08/2020 &
7/9/2020

10 IMU Visit to the Pilot Plant 02/09/2020

11 Finishing School & Career Virtual Talk 2020 14/09/2020

12 FOP Research Writing Camp No.1 24/09/2020

13 Faculty Strategic Planning 2020-2025 22/09/2020 &
28/9/2020

14 Webinar: Docking for Dummies - Theory and Docking 01/10/2020
Hands On

15 Minggu Haluansiswa | WOW (Week of Welcome) - Majlis 06/10/2020
Bersama Pelajar Baru

16 Webinar Career Sharing Session with Alumni Faculty of 31/10/2020
Pharmacy

17 White Coat Ceremony for UG students 16/11/2020

18 Virtual Dean’s List & Emerald Award Ceremony 2020 for UG 16/11/2020
students

19 Online Pharmily Gathering 2020 with UG students 17/11/2020

20 Marketing & Recruitment Centre (MRC) programme 19/11/2020
- UM Exclusive Webinar Series: Explore the World of
Pharmaceutical Wonders with Faculty of Pharmacy

21 Online training for Certification Unit - “Laboratory Quality 26-27/11/2020
Management Systems ISO/IEC 17025:2017”

22 Mobility Programme for UG students - Webinar: Coffee Talk 11/12/2020
with Pharmacists

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Highlights of the Faculty’s Research

Complementary and Alternative
Medicine Use in Patients with
Chronic Kidney Disease: What is
our Concern?

Noorasyikin Shamsuddin
Department of Clinical Pharmacy & Pharmacy Practice, Faculty of Pharmacy, University of
Malaya, 50603 Kuala Lumpur, Malaysia

Chronic kidney disease (CKD), also known as chronic kidney failure, is
defined as the presence of kidney damage with a diminished level of kidney
function. According to the Kidney Disease Improving Global Outcome
(KDIGO) Clinical Practice Guidelines (2013), CKD is defined as abnormalities
of the kidney structure or function, that is present for more than 3 months, with
health implications [1]. CKD has evolved to become a major global health issue.
It was estimated that 661,000 Americans have been diagnosed with kidney failure
[2]. Of these, 468,000 individuals are on dialysis, and around 193,000 Americans
are kidney transplant recipients. The number of cases in Malaysia has increased
by 2.5-fold with the total number of patients receiving dialysis recorded to be
13,356 cases in 2005 and continuing to rise to 34,767 cases in 2014 [3]. CKD
incidence in Malaysia is mainly due to diabetes (61%) and hypertension (18%). It
was interesting to note that around 15% of the cases were attributed to unknown
causes. It is plausible that the ingestion of nephrotoxic substances may contribute
to the idiopathic cause of CKD.

Complementary and alternative Despite the recommendation to
medicine (CAM) can be divided avoid herbal remedies and products,
into three main categories, as the use of this type of CAM has
outlined by the National Centre escalated among patients with CKD. A
for Complementary and Integrative large study by Osman et al. [4] in 1005
Health (NCCIH), as either natural kidney patients revealed that around
products, mind-body practices, and half of the study patients were using
other complementary approaches. The CAM, with a majority of them ingesting
KDIGO Clinical Practice Guidelines herbal and natural products. In another
(2013), recommends that patients with study by Zyoud et al. [5], it was reported
CKD should avoid the use of over-the- that 64% of haemodialysis patients
counter products and herbal remedies, are using CAM, particularly herbal
which are a major part of the CAM. therapies. In Malaysia, the prevalence

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of CAM use among patients with CKD Another classic example of herbs that
is reported to be 64.7% [6]. can induce nephrotoxicity is herbs from
the Aristolochia species. Additionally,
Looking at the high prevalence CKD patients commonly have some
of consumption of herbal remedies underlying cardiovascular problems.
in patients with CKD, what is our Among the herbs highlighted by Bagnis
concern? As highlighted by De Smet et al. [8] that should be taken with
[7], the health risks associated with precaution by patients with kidney
herbal remedies can be divided problems are Ginkgo biloba which
into two: inherent and acquired has the potential to cause bleeding
toxicity. Inherent toxicity of herbs is from interactions with anticoagulants
mostly associated with the biological such as warfarin and heparin; and St
constituents of the herb, while acquired John’s Wort which possesses hepatic
toxicity may happen due to external enzyme inducer properties; as well as
factors, such as contamination of dandelion and alfalfa which contain
herbal material, intended adulteration high amounts of potassium that can
of herbal medicine with prescription lead to hyperkalaemia.
medicine, drug-herbal compound
interactions, and lack of quality control Apart from herbs, other dietary
[7]. Lack of regulations governing the supplements, such as vitamins and
safety of herbal medicine may also minerals have been implicated with
cause the acquired toxicity of herbs. renal injury. A review carried out
Herbs with active compounds and with by Gabardi et al., (2007) [9] listed
pharmacological activities may also the common dietary supplements
contain toxic compounds. Therefore, that have the potential to cause
it is not surprising that some herbs nephrotoxicity. Vitamin C or ascorbic
may cause kidney injury. A review by acid has been reported to cause
Bagnis et al., [8] highlighted the renal nephrolithiasis secondary to oxaluria.
side effects of herbs and the potential Germanium, which is a chemical
hazards of herbs in patients with renal element commonly used in CAM for
disease. In their review, Bagnis et al. rheumatoid arthritis and osteoarthritis,
[8] described the mechanisms of herbs is associated with tubular degeneration
to cause hazards to the kidneys can and minor glomerular abnormalities.
be divided into four: (1) herbs that are Another common supplement with
properly identified, but with unknown the potential to cause renal injury is
or underestimated renal toxicity; L-lysine, which has been reported
(2) herbal plants contaminated with to cause Fanconi Syndrome and
heavy metals, hormones or drugs; (3) tubulointerstitial nephritis. Cranberry
herbal plants incorrectly identified, juice, which is commonly used in the
and (4) herbal plant interactions with treatment of urinary tract infection, can
conventional drugs. Some examples induce nephrolithiasis secondary to
of properly identified herbs with oxaluria.
underestimated renal toxicity are
traditional African herbs such as The presence of impurities, such as
Euphorbia matabelensis and Callilepsis heavy metals, bacteria and pesticides
laureola, which are traditionally are often reported in herbal products.
consumed as purgative but have been Heavy metals, such as arsenic and
reported to cause kidney damage. mercury, may present in herbs as the
result of polluted soil and irrigation
22 THE PANACEA

water. Heavy metals are generally References:
very toxic at a very low dose, non-
biodegradable and have a long 1. The Kidney Disease Improving Global
biological half-life. Consumption of Outcome (KDIGO). Kidney Disease
acute and chronic intoxication of heavy Improving Global Outcome (KDIGO)
metals may lead to nephropathies that 2012 Clinical Practice Guidelines for
may range from tubular dysfunction the Evaluation and Management of
to severe renal failure and fatalities Chronic Kidney Disease. Kidney. Int.,
[10]. A recent study by Shaikh Abdul Suppl 3,(2013).
Rahman & Aziz [11] on the adverse
drug reactions (ADR) of CAM in 2. National Institutes of Diabetes and
Malaysia revealed that CAM products Digestive and Kidney Diseases.
such as Chinese and Malay traditional Kidney Disease Statistics for the
medicine have caused around 26% United States n.d. https://www.niddk.
of serious ADR and 36 fatalities. The nih.gov/health-information/health-
most common ADR reported from the statistics/kidney-disease (accessed July
use of CAM were skin and appendages 10, 2017).
disorders (18.4%), followed by liver and
biliary system disorders (13.6%). The 3. Malaysian Society of Nephrology.
study revealed that urinary disorders, 22nd Report of the Malaysian Dialysis
which include kidney disorders were and Transplant Registry 2014. Kuala
the top five common systems affected Lumpur, Malaysia (2014).
by CAM. The authors pointed out
that unregistered CAM products were 4. N.A. Osman, S. M. Hassanein, M. M.
implicated in 70% of the death cases. Leil, M.M. NasrAllah, Complementary
and Alternative Medicine Use Among
The serious concern on the use Patients With Chronic Kidney Disease
of CAM products mainly lies in the and Kidney Transplant Recipients, J.
adverse consequences on the kidney Ren. Nutr., 25, 466 (2015).
and the impact can be worse in
patients with already impaired kidney 5. S. H. Zyoud, S.W. Al-Jabi, W.
functions. What is more alarming being M. Sweileh, G.H. Tabeeb, N.A.
that a high percentage of patients did Ayaseh, M.N. Sawafta, et al., Use
not disclose their use of CAM products of complementary and alternative
to their physicians [12]. It is high time medicines in haemodialysis patients:
for health care professionals to be more a cross-sectional study from Palestine,
vigilant on the use of herbal products BMC Complement. Altern. Med., 16,
among their patients, particularly 204 (2016).
patients with CKD. Routine queries
and explanations on the risk of CAM 6. N.F. Zakaria, M.T. Mohd Noor,
products are recommended to ensure R. Abdullah, Traditional and
patients are aware of the risks posed by complementary medicine use among
these products. Drug control authorities chronic haemodialysis patients: a
may enforce stricter regulation and nationwide cross-sectional study.
widen the post-marketing surveillance BMC Complement. Med. Ther., 21, 94
on herbal products to ensure the (2021).
safety of these products for public
consumption. 7. P.A. De Smet, Health risks of herbal
remedies. Drug Saf., 13, 81 (1995).

8. I. Bagnis, G. Deray, A. Baumelou,
M. Le Quintrec, J.L. Vanherweghem,
et al., Herbs and the kidney. Am. J.
Kidney Dis., 44, 1(2004).

9. S. Gabardi, K. Munz, C. Ulbricht,
A Review of Dietary Supplement–
Induced Renal Dysfunction. Clin. J.
Am. Soc. Nephrol., 2, 757 (2007).

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10. O. Barbier, G. Jacquillet, M.Tauc, M.
Cougnon, P. Poujeol, Effect of Heavy
Metals on, and Handling by, the
Kidney. Nephron. Physiol. 99, 105
(2005).

11. S. Shaikh Abdul Rahman, Z. Aziz.
Complementary and alternative
medicine: Pharmacovigilance in
Malaysia and predictors of serious
adverse reactions, J. Clin. Pharm. Ther.,
45, 5 (2020).

12. L. Alanizy, K. Almatham, A. Al
Basheer, I. Al Fayyad, Complementary
and alternative medicine practice
among saudi patients with chronic
kidney disease: A cross-sectional
study. Int. J. Nephrol. Renovasc. Dis.,
13, 11 (2020).

24 THE PANACEA

Virtual Screening of Potential
Tripeptide Inhibitors Towards Ns3
Serine Protease of Dengue Virus

Jonathan Ho1, H.Y Woon, C.H Heh
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Malaya,
50603 Kuala Lumpur, Malaysia

Dengue is a mosquito-borne viral infection caused by dengue virus (DENV),
a flavivirus under Flaviviridae [1]. It is one of the most prominent arthropod-
borne viral infections, with mainly Aedes aegypti and Aedes albopictus as
vectors, that infects about 390 million people every year [2].

Despite the emergence of the with the amino acid sequence Arg-Arg-
tetravalent dengue vaccine (CYD- Gln showed the most potential in silico
TDV) [3], it shows mixed protective DENV NS3 serine protease inhibition
results and there is no other effective with the binding energy of -7.0 kcal/
alternative antiviral treatment [4, 5]. mol and percentage of binding of 14%.
Thus, an antiviral agent against dengue On the other hand, D-tripeptide with
virus (DENV) is still in dire need. As the amino acid sequence Trp-Glu-Phe
DENV-3 NS3 serine protease plays showed the most potential in silico
a crucial role in viral replication [6], DENV NS3 serine protease inhibition
it could be a potential drug target with the binding energy of -8.5 kcal/
for antiviral agents. Recently, there mol and percentage of binding of
is a study shows that the tripeptide 14%. However, further in vitro study
can act as an inhibitor towards the is required to verify the potential
DENV NS3 serine protease [7]. In this inhibition of L- and D-tripeptides
research, we carried out an in silico towards DENV NS3 serine protease.
discovery of potential tripeptides
inhibitors towards NS3 serine protease References
of DENV via virtual screening. The
crystal structure of DENV NS3 serine 1. Screaton, G., et al., Nature Reviews
protease, 3U1I was first retrieved Immunology. 15, 12, 745-759 (2015).
from the Protein Data Bank (PDB)
with benzoyl-norleucine-Lys-Arg-Arg- 2. Bhatt, S., et al., Nature. 496, 7446,
aldehyde [(BEZ)(NLE)KR(OAR)] as the 504-7 (2013).
standard inhibitor. Virtual screening
was performed involving 8,000 3. Guy, B., et al., Vaccine. 33, 50, 7100-
L-tripeptides and 8,000 D-tripeptides 11 (2015).
using AutoDock Vina software [8] with
100 exhaustiveness. Then, the analysis 4. Capeding, M.R., et al., Lancet. 384,
of the binding interaction for the 9951, 1358-65 (2014).
tripeptides was done using Discovery
Studio 4.5. As a result, L-tripeptide 5. Villar, L., et al., N Engl J Med. 372, 2,
113-23 (2015).

6. Lescar, J., et al., Antiviral Res. 80, 2,
94-101 (2008).

7. Schuller, A., et al., Antiviral Research.
92, 1, 96-101 (2011).

8. Trott, O. and A.J. Olson, J Comput
Chem. 31, 2, 455-61 (2010).

THE PANACEA 25

The Future of Nanotherapeutics in
Anti-Cancer Drug Delivery

Saw, W. S.a, Anasamy, T.a, Kiew, L. V.b, Chung, L. Y.a
aDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Universiti Malaya, 50603
Kuala Lumpur, Malaysia
bDepartment of Pharmacology, Faculty of Medicine, Universiti Malaya, 50603 Kuala
Lumpur, Malaysia

In the past three decades, nano delivery systems are often applied to anti-cancer
drug delivery to overcome the common setbacks of conventional chemotherapy
such as nonspecific bio-distribution, toxicity and poor targeting. The clinical
chemo drugs were integrated into various bio-compatible nanocarriers and
delivered towards the target region tumour.

The design of the nano-sized Fig. 1. Smart autonomous delivery systems
carriers has demonstrated improvement
in i) chemo drug solubility in blood, ii) disguise nanoparticles with natural
selectivity against cancerous cells, and cells’ functions. Nanoparticles coated
iii) protection of drug against premature with red blood cell (RBC) or cancer
bio-degradation and excretion. cell membranes that express CD47,
However, despite the promising pre- ̶ an important surface marker, help
clinical data, the majority of the nano the nanoparticles prolong blood
delivery systems heavily rely on blood circulation time by evading the
circulation and are often impeded by immune system. The CD47 binds to the
challenges such as protein adsorption signal regulatory protein α. It conveys a
and off-target drug accumulation “do not eat me” signal to immune cells,
in major organs during the delivery
process. Thus, researchers started to
explore the next generation of self-
directed nano delivery systems that can
function without aligning with the blood
flow direction. Different strategies,
including biomimetic approach, DNA
origami, bacterial sensing, and external
stimuli, have been implemented to
design smart autonomous delivery
systems (nanobots) that possess
multiple functionalities to achieve
sophisticated targeting properties (Fig.
1).

Biomimetic targeting systems
utilise cell membranes of various cells,
including erythrocytes, leukocytes,
cancer cells, and stem cells, to

26 THE PANACEA

thus helping the RBC and cancer cell The strategy of combining
membrane-coated nanocarriers evade functional nanocarriers with bacterial
phagocytosis. Like RBC, macrophage biological systems provides an efficient
membrane-coated nanoparticles also nanohybrid system with a tumour-
exhibited a prolonged circulation targeting advantage. Bacteria are
time, but they have a greater ability to naturally attracted to oxygen-deficient,
cross vascular barriers and penetrate nutrient-rich, and immuno-suppressive
deep tumour regions. The 4-integrin tumour environments. Furthermore,
of the macrophages interacts with the they possess self-propulsion abilities to
vascular cell adhesion molecule-1 penetrate the previously unattainable
of the cancer cells, allowing a highly tumour regions. Researchers are either
functional active targeting of the encapsulating the nanocarriers within
macrophages to the cancer cells. bacteria or attaching them to the
bacteria’s surface. These nanohybrid
The idea of DNA nanorobots for swimmers will then migrate to the
biological applications was raised targeted areas and being uptaken by
in the last two decades. The core tumour cells. A recent example features
technology to create DNA nanorobots, the tumour-targeting Salmonella
known as ‘DNA Origami’, was named typhimurium’s functional capabilities
after the Japanese art of folding papers to assist the delivery of polymeric
into decorative figures. By utilising the nanocarriers into the 4T1 breast tumour.
DNA base pair properties, researchers These nanohybrid swimmers improved
created the self-assemble nanorobot intratumoral nanoparticle retention
(molecular spider) and controlled by an astonishing 100-fold compared
its directional movement on a to the conventional nanocarrier [1].
complementary substrate track. The Overall, this nanohybrid strategy
nanorobot was then equipped with the unlocks a new paradigm in cancer
programmable cargo donating device treatment by enhancing the therapeutic
for autonomous movement and cargo index of chemo drugs while minimising
delivery attempts. non-specific toxicities.

In recent years, an international Inspired by the locomotions of
team of scientists has created the microorganisms, researchers
a programmable DNA origami have developed nanocarriers with
nanorobot that unfolds itself precisely different propulsion mechanisms.
at the tumour vascular endothelium These nanocarriers actuate by
to deliver blood-clotting protein, external stimuli and are powered by
thrombin. Upon release of thrombin, biocompatible energy sources, mainly
the formation of blood clots effectively magnetism and ultrasound energy.
blocks the supply lifelines for the Magnetic nanocarriers have been
tumour, causing the shrinkage of the developed for localised chemo drug
existing tumour while inhibiting the delivery. Using the external magnetic
metastasis. This first-ever successful field guidance system, researchers
demonstration of thrombin-delivery can direct the magnetic nanocarriers
DNA nanorobots in in vivo stage into precisely targeted tumour regions
marked the significant milestones in and even increase the transport of the
the evolution and application of DNA nanocarriers across the blood-brain
nanotechnology. barrier. Magnetic directed nanocarriers

THE PANACEA 27

are important candidates in modern References
cancer treatment regimes and are
currently undergoing clinical trials 1. Suh, S.; Jo, A.; Traore, M. A.;
for efficacy evaluation. Contrary, Zhan, Y.; Coutermarsh‐Ott, S.
the ultrasound propulsion of rod- L.; Ringel‐Scaia, V. M.; Allen,
shaped gold nanoparticles was first I. C.; Davis, R. M.; Behkam, B.
demonstrated in HeLa cervical cancer Nanoscale Bacteria‐Enabled
cells in 2014. The gold nanorod can Autonomous Drug Delivery
perform directional motion and spin System (Nanobeads) Enhances
without causing cell damage, and this Intratumoral Transport of
ability has shown great potential for Nanomedicine. Advanced
multiple functionalities in intracellular Science 2019, 6 (3), 1801309.
operations. Additionally, ultrasound 2. Saw, W. S.; Anasamy, T.; Foo, Y. Y.;
can release encapsulated chemo drugs Kwa, Y. C.; Kue, C. S.; Yeong, C.
from carriers (nanobubbles) within H.; Kiew, L. V.; Lee, H. B.; Chung,
cancer cells. Till then, the chemo drug L. Y. Delivery of Nanoconstructs
will be safely encapsulated within the in Cancer Therapy: Challenges
nanobubbles to reduce adverse side and Therapeutic Opportunities.
effects upon administration. Advanced Therapeutics 2021, 4
(3), 2000206.
Nanotechnology made its
appearance in drug delivery with the
hope to achieve the ‘magic bullet’
concept proposed by Paul Erhlich,
as it acted as the ideal drug carrier
which could reach the correct target
without affecting the non-target organs.
However, this concept has evolved
into the ‘therapeutic missile’ strategy
involving the adaptable autonomous
drug delivery system. They can steer
towards the targeted location while
overcoming biological barriers in the
journey, such as blood flow direction
and mononuclear phagocyte system
[2]. The autonomous nanobots are
envisioned to significantly impact
cancer treatment outcomes by slowly
ticking the ideal drug delivery carrier
checklist.

28 THE PANACEA

Reprocess and Repurpose
of Active Pharmaceutical
Ingredients (Apis) from Expired
Pharmaceutical Products (Epps)
-An Eco-Friendly Approach- Mini
Review

B.V.S Lokesh
Senior Lecturer, Department of Pharmaceutical Chemistry, Universiti Malaya, 50603 Kuala
Lumpur, Malaysia.

Background systems at ground level. In a study, it
was examined the role of pharmacist to
In recent years, it has been evident identify the sources of pharmaceutical
that some pharmaceuticals may waste, disposal costs, secured disposal
possess certain potency even beyond methods, effects of inappropriate
their date of expiration. Despite this disposal, it was also discussed how to
statement, there are no approved mitigate such effects by creating public
guidelines or amendments in the United awareness on disposal patterns and
States Federal Drug and Administration strategies. (Nyaga M N et al., 2020)
(USFDA) to use expired pharmaceutical
products (EPPs) for other purposes, but It has also been reported that
not for human consumption. On the traces of pharmaceuticals and
other hand, the scientific community pharmaceutical products are found
and drug regulatory authorities in municipal groundwaters, rivers,
continue to seek scientific attention the Baltic region of various coastal
from medical professionals about the corridors and aquatic environments.
status of EPPs. This signifies that disposal of EPPs
The American Medical Association inappropriately into sinks, toilet
(AMA) and the Food and Drug flushing, even municipal garbage leads
Administration (FDA) do not to trigger toxicity by these traces of
recommend dosing of these EPPs to pharmaceuticals, their metabolites,
patients due to high probability of and toxic expired products, which flow
unknown adverse side effects and into the ground water, potable water,
encourage further research to be lakes, rivers and ultimately to the sea.
done to prove these EPPs are safe for This was supported and reported by a
human use (Culbertson, 2011). Apart recent study to find the polychlorinated
from this, improperly disposed of biphenyls (PCB) levels in fish. In this
EPPs pose a significant threat to the study, total PCBs concentration was
environment and a high risk of toxicity quantified, including 12 congeners
for food corps, drinking water, aquatic

THE PANACEA 29

and different types of toxic PCBs, pharmaceutical products under Code of
which are highly toxic to humans. A Federal Regulations (CFR), United States
major industrial contaminant (PCB Food and Drug Administration policies
126) which is also the most toxic and Malaysian Regulatory guidelines
congener was detected in the samples (NPRA guidelines, 2011). Reuse of
at relatively low concentrations in the EPPs was facilitated by extracting APIs
muscle tissue of fish species collected from them and their utilisation for the
along the Baltic region of the Strait of synthesis of laboratory chemicals or
Malacca (SOM) (Mohamad, 2012). useful compounds as disinfectants in
Many semisynthetic organic recent reports. In their study, expired
chemicals such as estrogenic aspirin tablets were taken and further
hormones (Estrone and 17 -estradiol) converted into salicylic acid and upon
were introduced into the environment. decarboxylation to give phenol as an
Sources of endocrine-disrupting effective bacteriostatic and bactericidal
compounds (EDCs) include natural agent. Proper disposal method was
and synthetic hormones, personal- designed for expired aspirin tablets
care products, pesticides, phthalates, without throwing them directly into the
alkylphenol ethoxylate surfactants, environment. (Sharma, 2019).
flame retardants, dioxins, coplanar
polychlorinated biphenyls (PCBs), In a separate comprehensive
parabens, bisphenol A, and organotin review, it was emphasized on the
were traced in the aqua environment. shelf life, manufacturer’s guarantee for
Various analytical methods were also clinical safety and efficacy until the
reported for their trends to analyse expiry date of drug products as it was
targeted and nontargeted organic well recorded to the scientific world
compounds in complex matrices that the medication is used within its
to support and alarm the danger shelf-life, for its maximum effectiveness
by reporting traces in coastal water and safety. Recent studies conducted by
samples from time to time. However, the U.S. Food and Drug Administration
appropriate analytical methods are (USFDA) over 100 prescription and
essential to identify, detect and quantify over-the-counter products. Among all,
these toxic chemicals in water samples 90 drug products have been exhibited
for environment monitoring and still safe and effective even after 15
remedial action (Richardson, 2011, years past their expiration dates, if
Zoraida, 2013). Regulatory authorities properly stored. It was also reported
insist on following regulatory guidelines that when a drug product gets expires,
of active pharmaceutical ingredients it may contain APIs up to 90% potency.
(APIs). Hence pharmaceutical products APIs could be extracted by suitable
are well monitored to follow strictly extraction techniques for isolation and
such guidelines before approval quantification by chromatographic
and adhere to the guidelines for analytical techniques for the purpose
products approvals. These guidelines of recycling into useful synthetic
are specified for assessing chemical intermediates or active drugs. This
composition, purity, impurity profiling, approach would remain cost-effective
stability-indicating assays(SIA), from keeping in view of their industrial
and shelf life for APIs as well as applicability and commercial benefits
as well as eco-friendly approach

30 THE PANACEA

without disposal of these EPPs into drug development and for other
effluent wastes groundwater levels in pharmaceutical importance. This
the environment (Basha, 2015). simple approach can save time,
be more economical, less threat
Discussion to the environment without toxic
disposals of these EPPs, a source of
It was clearly specified in the USFDA laboratory standards for research
and regulatory guidelines that these and development, meets sustained
EPPs do not possess 100% purity development goals.
beyond their expiration dates. However,
they considered to be expired, when Various physicochemical, analytical,
their date of expiry is over though instrumental, chromatographic, and
there is no change in the physical spectroscopic techniques are best
decomposition chemical degradation utilised in various research laboratories
and their stability data is still supportive to extract, detect, and estimate the purity
as per shelf life, they are not intended levels of APIs from EPPs as a recovery
for human use anymore. However, process.The cost of APIs is rising sky high,
active pharmaceutical ingrediend and any funding agencies, industrialists
ts (APIs) can be recovered into their and research scientists would make
purest form by extraction in 100% a point of serious worry since their
composition from EPPs. The present availability even in small quantities
review emphasises on the recycle, precious for research, cost-saving and
recrystallise, purify, and repurpose industrial application. The extracted APIs
of APIs from EPPs by extracting in purest form would serve as laboratory
individual API in its purest form with standards, starting materials or precursors
an active composition and good yield for the synthesis of new compounds,
by a sustainable and green chemistry experimental standards in the research
approach. These active pharmaceutical of drug discovery and development. This
ingredients are tested for their stability, process supports against environmental
composition, purity, and repurpose disposal of EPPs without proper waste
for their pharmaceutical importance treatment, reduces pollution, eradicates
clinically. It is recorded in many contamination of pharmaceuticals into
reference books that any drug product environmental waters, reduces cost of
is intended to lose its stability and shelf active pharmaceutical standards (APIs)
life, if the potency is below 90%. In since they serve as secondary standards
other words, the API may be present in for sustained research and development,
its purest form less than 90%. APIs can by reducing laboratory waste to meet
always be extracted in their pure form, the goals of green technological and
irrespective of how much quantity is laboratory practices.
recovered from EPPs. For example, if a
drug product contains 500 mg of API as Conclusion
a labelled dose, minimum of 400 mg
of its pure drug from its EPPs can be It is clearly indicated and suggested
recovered to further recycle, repurpose, that a survey conducted on first and
and reassess of its pharmaceutical most 100 highly prescribed drug
importance as a laboratory standard,
precursor for synthesis drug discovery,

THE PANACEA 31

products in Malaysia and their disposal 7. Sosa-Ferrera, Z., Mahugo-
patterns. This project can be developed Santana, C., & Santana-
to tie up with Industry to collect EPPs Rodríguez, J. J. BioMed research
and reprocess in our sophisticated international, (2013)
analytical laboratories into laboratory
working standards, experimental 8. World Health Organization,
precursors, and even their degradation International Pharmaceutical
and impurity standards in purest form. Association, & International
These libraries of the purest APIs from Solid Waste Association.
EPPs can be further utilized for the (1999). Guidelines for safe disposal
synthesis of new compounds, tested of unwanted pharmaceuticals in
for their safety and clinical efficacy and after emergencies (No. WHO/
to monitor the stability for extension EDM/PAR/99.2). World Health
of shelf life. In collaboration with Organization.
pharmaceutical industries, it can
be a successful approach to meet 9. Sivasankaran, P., Elmutaz, B.
eco-friendly laboratory approach, M., Ganesan, N., & Durai, R.
green laboratory and meet sustain (2019). Storage and safe disposal
development goals. of unwanted/unused and expired
medicines: A Descriptive cross-
References sectional survey among Indian
rural population. Journal of Young
1. Basha, S. C., Babu, K. R., Madhu, Pharmacists, 11(1), 97.
M., Kumar, Y. P., & Gopinath, C. J.
10. Nyaga, M. N., Nyagah, D. M., &
Njagi, A. (2020). Pharmaceutical
waste: Overview, management,
and impact of improper disposal.

Global Trends in Pharm. Sci., 6(2),
2596-2599 (2015).
2. Culbertson N.T. J Spec Oper
Med., 11(2):1-6(2011). PMID:
21706454.
3. Mohamad, A., Azlan, A., Razman,
M. R., Ramli, N. A., & Latiff, A. A.
(2012). Level of Polychlorinated
Biphenyls (PCBs) in selected
marine fish (pelagic) from Straits
of Malacca.  Pertanika J. Trop.
Agric. Sci, 35(2), 351-362.
4. NPRA guidelines (2012).
Regulatory Control of Active
Pharmaceutical Ingredients,
Appendix 14, version 1.
5. Richardson, S.D., Ternes,
T.A. Analytical Chemistry
83(12):4616–4648(2011).
6. Sharma, M. M., & Chaudhary, M.
A. K. D. A. Int. J. Engg. Res.& Tech.
8(6):276-298(2019).

32 THE PANACEA

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promoter of health
and is as friendly to the
mind as to the body.

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ADDISON

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affinity towards self-
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