ADVANCES IN NATURAL

PRODUCT RESEARCH

PROF. SYED MOHSIN SAHIL JAMALULLAIL

Dean of Research
Biomedical & Health Science Research Platform
smohsin@kb.usm.my
What is natural product?
 Natural products are chemical compounds, materials or substances produced by
living organisms.

 They are found in nature and some of them do have substantial pharmacological or
biological activity.

 Natural products has been used for the development of pharmaceutical drugs via
drug discovery and drug design efforts as well as other useful purposes (food, food
supplement etc.) to serve human needs.

 It still offers a vast, virtually untapped reservoir of new chemical compounds or entity
with many potential uses.

 Chemical diversity in nature is based on biological and geographical diversity, so

researchers travel around the world obtaining samples to analyze and evaluate in
drug discovery screens or bioassays. This effort to search for natural products is
known as bioprospecting.  

 Finding of appropriate usage for natural product is not so easy since it require a
broad array of scientists who can research into many different aspect to substantiate
the findings and to be acceptable to to the public. 
Plant Kingdom Marine World

Sources of
Natural
Product

Animal Kingdom
Microbial World

A crude (untreated) extract from any one of

these sources typically contains novel and
structurally diverse chemical compounds
The plant kingdom
 Plants have always been a rich source of lead compounds (e.g. morphine,
cocaine, digitalis, quinine, tubocurarine, nicotine, colchicine and muscarine).

 Many of these lead compounds are useful drugs in themselves (e.g.

morphine and quinine), and others have been the basis for synthetic drugs
(e.g. local anaesthetics developed from cocaine).

 Its provide a large bank of rich, complex and highly varied structures of lead
compound which are unlikely to be synthesized in laboratories.

 Even today, the number of plants that have been extensively studied is
relatively very few and the vast majority have not been studied at all and in
fact in Malaysia there are still plants which have not been taxonomically
named.

 Clinically useful drugs which have been recently isolated from plants include
the anticancer agent paclitaxel (Taxol) from the yew tree, and the
antimalarial agent artemisinin from Artemisia annua.
The microbial world
 Microorganisms such as bacteria and fungi have been invaluable for discovering
drugs and lead compounds
- produce a large variety of antimicrobial agents which have evolved to give their
hosts an advantage over their competitors in the microbiological world.

 The screening of microorganisms became highly popular after the discovery of

penicillin.

 Antibacterial agents such as the cephalosporins, tetracyclines, aminoglycosides,

rifamycins, and chloramphenicol.

 Lead compounds in other fields of medicine

 asperlicin - isolated from Aspergillus alliaceus - is a novel antagonist of a
peptide hormone called cholecystokinin (CCK) which is involved in the control of
appetite.
 CCK acts as a neurotransmitter in the brain and is thought to be involved in
panic attacks. Analogues of asperlicin may therefore have potential in treating anxiety.

 Fungal metabolites:
 Lovastatin - the lead compound for a series of drugs that lower cholesterol levels
 ciclosporin - used to suppress the immune response after transplantation operations.
The marine world

 In recent years, there has been a great interest in finding lead compounds
from marine sources.

 Coral, sponges, fish, and marine microorganisms have a wealth of

biologically potent chemicals with interesting inflammatory, antiviral, and
anticancer activity.

 For example, curacin A is obtained from a marine cyanobacterium and

shows potent antitumor activity.

 Other antitumor agents derived from marine sources include eleutherobin,

discodermolide, bryostatins, dolostatins, and cephalostatins.
Animal Kingdom
 Animals can sometimes be a source of new lead compounds.

 For example, The Malayan Pit Viper (Anchistrodon rodustroma) venum is

the lead material that help produce the anticoagulant Arvin or Ancrod.

 Many hormones were initially derived from animals before the advent of
the recombinant products.

 A series of antibiotic peptides were extracted from the skin of the

African clawed frog and a potent analgesic compound called epibatidine
was obtained from the skin extracts of the Ecuadorian poison frog.
Why natural product
research?
-Antioxidant; anti-aging
-Cosmetics
-Cancer agents
-Drug discovery
-Food and beverage
-Dietary supplement
-Recombinant protein
-Resins and building materials
-Supply of biomass
-Biofuel
etc
 DNA

Plants Microorganism

Proteins

Natural products
New bioassay methods
Past study…
The assays that were in use
were primarily animal models of
human diseases.
By today's standards, they were
slow, expensive, difficult to
interpret at times, and not very
selective, but sometimes
necessary to look at effects on
the whole organism. This
preclinical studies are still
necessary!
Combination with in vitro
antibacterial, antifungal, antiviral and
antiparasitic assays - economically
feasible to screen large numbers of
substances in a wide range of
assays, and in a relatively short
time.
Present study…
Mode of action assays
The effect of a compound on a
discrete biochemical event is
measured and compared with a
similar event in the absence of test
compound.
This event may be the binding of a
ligand to its receptor, or the activity of
an enzyme, or the transcription of a
gene in a cultured cell, or any of a
number of other kinds of measurable
biochemical phenomena.
Characteristics: fast, quantitative, and
easy to perform, making them ideal
for miniaturization and automation,
relatively inexpensive once
appropriately miniaturized
 Advances in chemical methods
 Natural products research is not low-cost but it offers an extremely high level of
molecular diversity.

 The advances in assay technology have been a necessary factor in the

resurgence of interest in natural products.

 The advent and subsequent development in chemistry and chemical

instrumentation such as;

-High performance liquid chromatography (HPLC),

-High performance centrifugal countercurrent chromatography (HPCCC),
-Capillary zone electrophoresis (CZE)
-High resolution mass spectrometry (HRMS)
-High field nuclear magnetic resonance spectrometry (NMR)
-X-ray crystallography

 These instruments have allowed the chemist to isolate sub milligram quantities
of new compounds, and confidently be able to fully characterize them and
identify their structures
HPLC in natural product research
Primary focus of pharmaceutical industry
 The main thrust of the research at a large pharmaceutical
corporation is directed towards the discovery and development of
new drugs from novel chemical entity.

 Natural products research is a part, and in truth a small part, of the

discovery process. The screening of natural products is one of the
earliest steps in drug discovery, namely 'lead' identification.

‘In the 1970s, 25% of all drugs dispensed in the USA contained
compounds derived from flowering plants, with an even greater
proportion of phytochemicals used as drugs worldwide; 16% of
drugs dispensed in the USA were derived from microbial and
animal sources. Even at the dawn of the twenty-first century,
11% of the 252 drugs considered as basic and essential by the
World Health Organization were exclusively of flowering plant
origin’.

Review Article TRENDS in Biotechnology (2002). Plants and human health in the twenty-first century.
Vol.20 (no. 12)
Plant-derived drug and projected worldwide sale

TRENDS in Biotechnology (2002). Plants and human health in the twenty-first century. Vol.20 (12)
Natural product-based antitumor
drugs discovery

Vishnu Ji Ram and Seema Kumari (2001). Natural Products of Plant Origin as Anticancer Agents. Drug News Perspect vol 14(8): page
465
Venoms and toxins
 From animals, plants, insect and microorganisms are extremely potent because they
often have very specific interactions with a macromolecular target in the body.

 As a result, they have been proved as an important tools in studying receptors,

ion channels, and enzymes.

 Many of these toxins are polypeptides (e.g. ɑ-bungarotoxin from cobras). However,
non-peptide toxins such as tetrodotoxin from the puffer fish are also extremely potent.

 Venoms and toxins have been used as lead compounds in the development of
novel drugs. For example, teprotide, a peptide isolated from the venom of the
Brazilian viper, was the lead compound for the development of the antihypertensive
agents cilazapril and captopril.

 The neurotoxins from Clostridium botulinum are responsible for serious

food poisoning (botulism), but they have a clinical use as well. They can be injected
into specific muscles (such as those controlling the eyelid) to prevent muscle spasm.
These toxins prevent cholinergic transmission and could well prove a lead for the
development of novel anticholinergic drugs.
 Natural cosmetic product
 Natural cosmetics have become a major trend in recent
years – not harmful to the human health?

 The natural cosmetics are made from plants, roots,

herbs and minerals.
-soap
-skin care creams and lotions
-shampoos
-hair color, henna
-perfumes, fragrances
-tooth paste, mouth wash
-cleansing creams
-anti-aging

 Sources: Aloe vera, Apricot, Bees wax, Bentonite

(bentonite clay), Celendula Officinalis, Cinnamon (ceylon
cinnamon), Chamomile (babuna), Eucalyptus (blue
gum), Grape seeds, Lavender oil, Lemon grass,
Spearmint (mentha spicata), Mint arvensis, Nettle
leaves, Neem tree, Patchouli oil, Rose petals, rosemary,
Safflower, Walnut etc
 Natural Food and Beverage
 Consumers demand has led specialty retailers to expand
natural/organic products departments and increase their focus on
the category

 40% of consumers currently use natural product at least

occasionally, according to the market research firm, The Hartmant
Group.

 Retail sales of organic products in 2001 are projected to be about

$9.3 billion and in 2005, organic sales alone are expected to reach
nearly $20 billion.

 Engineered functional food

 Recent advances in functional plant foods include;

 increasing vitamin E content in plants following initial
demonstrations in Arabidopsis
 selecting high lycopene or vitamin C tomatoes
 Metabolic engineering of legumes and tomatoes for high
content of bioflavonoids, known for their antioxidant,
anticancer and estrogenic properties
 possible uses of thioredoxin to decrease allergenicity of foods

Natural Products Research Report, Organic & Soy Sales Lead Category (2001). Michelle Moran.
Natural dietary supplements
 General public often considers botanical supplements
natural and safe alternatives to conventional synthetic
pharmaceuticals
– there is relatively little scientific evidence behind this believe..

 Lot to be done to improve the efficacy, image and science behind

botanical dietary supplements.

 Almost no sustained R&D efforts directed towards creating credible

product pipelines, quality control measures and discovery platform
of this natural dietary supplements.
Some of the dietary supplements sold in the market

 Echinacea purpurea, L. angustifolia, DC. and pallida Nutt.

- Respiratory infections, immunostimulant

 Panax ginseng, L.A. Mey (ginseng)

- Fatigue and stress, high cholesterol, diabetes, gastro- intestinal disorders

 Serenoa repens (W. Bartam) Small (saw palmetto)

- Benign prostatic hyperplasia (BPH), inflamations, impotence

 Ginkgo biloba L.
- Dementia, cognitive decline, mental fatigue

 Hypericum perforatum L. (St John's wort)

- Mild and moderate depression, epilepsy

 Valeriana officinalis L. (valerian)

- Sleep improvements, anxiety, hypertension

 Allium sativum L.(garlic)

- Cancer, high cholesterol, diabetes, arteriosclerosis, hypertension,
respiratory infections
Supply of biomass
 Biomass, a renewable energy source, is biological material derived from
living, or recently living organisms.
 commonly plant matter grown to generate electricity or produce heat.
 also includes plant or animal matter used for production of fibers or
chemicals.
 may also include biodegradable wastes that can be burnt as fuel.

 Industrial biomass can be grown from numerous types of plants, including

miscanthus, switchgrass, hemp, corn, poplar, willow, sorghum, sugarcane,
and a variety of tree species, ranging from eucalyptus to oil palm (palm oil).

 Research: Biomass conversion process to useful energy

 Chemical conversion
 Biochemical conversion
Specialty chemicals
 An area of study which malaysians have
not really considered in any great details
 Potentially lucrative area in the era of
biotechnological advancement
 E.g. inhibitors, promoters in specific
reaction sequences etc.
-THANK YOU-