Keynote B2 - Advances in Natural Product Research

8/9/2019 Keynote B2 - Advances in Natural Product Research

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ADVANCES IN NATURALPRODUCT RESEARCH

PROF. SYED MOHSIN SAHIL JAMALULLAILDean of ResearchBiomedical & Health Science Research [email protected]


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What is natural product?

Natural products are chemical compounds, materials or substances produced byliving organisms.

They are found in nature and some of them do have substantial pharmacological orbiological activity.

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

It still offers a vast, virtually untapped reservoir ofnew chemical compounds or entitywith 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 indrug discovery screens orbioassays. This effort to search for natural products isknown as bioprospecting.

Finding of appropriate usage for natural product is not so easy since it require abroad array of scientists who can research into many different aspect to substantiatethe findings and to be acceptable to to the public.


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Sources ofNaturalProduct

Plant Kingdom

MicrobialWorld

MarineWorld

Animal Kingdom

A crude (untreated) extract from any one of thesesources typically contains novel and structurally

diverse chemical compounds


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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 leadcompound which are unlikely to be synthesized in laboratories.

Even today, the number of plants that have been extensively studied isrelatively 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 taxonomicallynamed.

Clinically useful drugs which have been recently isolated from plants includethe anticanceragent paclitaxel (Taxol) from the yew tree, and theantimalarial agent artemisinin fromArtemisia annua.


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The microbial world

Microorganisms such as bacteria and fungi have been invaluable for discoveringdrugs and lead compounds- produce a large variety of antimicrobial agents which have evolved to give theirhosts an advantage over their competitors in the microbiological world.

The screening of microorganisms became highly popular after the discovery ofpenicillin.

Antibacterial agents such as the cephalosporins, tetracyclines, aminoglycosides,rifamycins, and chloramphenicol.

Lead compounds in other fields ofmedicine asperlicin - isolated from Aspergillus alliaceus - is a novel antagonist of a peptide

hormone called cholecystokinin (CCK) which is involved in the control ofappetite.

CCK acts as a neurotransmitterin the brain and is thought to be involved in panicattacks. Analogues of

asperlicin may therefore have potential in treating anxiety.

Fungal metabolites: Lovastatin - the lead compound for a series of drugs that lowercholesterol levels ciclosporin - used to suppress the immune response aftertransplantation operations.


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The marine world

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

Coral, sponges, fish, and marine microorganisms have a wealth ofbiologically potent chemicals with interesting inflammatory, antiviral, andanticanceractivity.

For example, curacin A is obtained from a marine cyanobacterium andshows potent antitumoractivity.

Other antitumor agents derived from marine sources include eleutherobin,

discodermolide, bryostatins, dolostatins, and cephalostatins.


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Animal Kingdom

Animals can sometimes be a source of new lead compounds.

For example, The Malayan Pit Viper (Anchistrodon rodustroma) venum isthe lead material that help produce the anticoagulantArvin orAncrod.

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

A series ofantibiotic peptides were extracted from the skin of theAfricanclawed frog and a potent analgesic compound called epibatidine wasobtained from the skin extracts of the Ecuadorian poison frog.


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Why natural productresearch?

-Antioxidant; anti-aging-Cosmetics-Cancer agents-Drug discovery-Food and beverage-Dietary supplement-Recombinant protein

-Resins and building materials-Supply of biomass-Biofueletc


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MicroorganismPlants

DNA

Proteins

Natural products


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New bioassay methods

Present study

Mode of action assaysThe effect of a compound on adiscrete biochemical event is

measured and compared with asimilar event in the absence of test

compound.

This event may be the binding of aligand to its receptor, or the activity ofan enzyme, or the transcription of agene in a cultured cell, or any of a

number of other kinds of measurablebiochemical phenomena.

Characteristics: fast, quantitative, andeasy to perform, making them idealfor miniaturization and automation,

relatively inexpensive onceappropriately miniaturized

Past study

The assays that were in usewere primarily animal models of

human diseases.

By today's standards, they wereslow, expensive, difficult to

interpret at times, and not veryselective, but sometimes

necessary to look at effects onthe whole organism. Thispreclinical studies are still

necessary!

Combination with in vitroantibacterial, antifungal, antiviral andantiparasitic assays - economicallyfeasible to screen large numbers of

substances in a wide range ofassays, and in a relatively short time.


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Advances in chemical methods

Natural products research is not low-cost but it offers an extremely high level ofmolecular diversity.

The advances in assay technology have been a necessary factor in theresurgence of interest in natural products.

The advent and subsequent development in chemistry and chemicalinstrumentation 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 quantitiesof new compounds, and confidently be able to fully characterize them andidentify their structures


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HPLC in natural product research


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Primary focus of pharmaceutical industry

The main thrust of the research at a large pharmaceuticalcorporation is directed towards the discovery and development ofnew 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 theearliest steps in drug discovery, namely 'lead' identification.

In the 1970s, 25% of all drugs dispensed in the USA containedcompounds derived from flowering plants, with an even greaterproportion of phytochemicals used as drugs worldwide; 16% of

drugs dispensed in the USA were derived from microbial andanimal sources. Even at the dawn of the twenty-first century,11% of the 252 drugs considered as basic and essential by theWorld Health Organization were exclusively of flowering plantorigin.

ReviewArticle TRENDS in Biotechnology (2002). Plants and human health in the twenty-first century.Vol.20 (no. 12)


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Plant-derived drug and projected worldwide sale

TRENDS in Biotechnology (2002). Plants and human health in the twenty-first century. Vol.20 (12)


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Natural product-based antitumordrugs discovery

Vishnu Ji Ram and Seema Kumari (2001). Natural Products of Plant Origin as Anticancer Agents.DrugNews Perspectvol 14(8): page 465


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Venoms and toxins

From animals, plants, insect and microorganisms are extremely potent because theyoften have very specific interactions with a macromoleculartarget in the body.

As a result, they have been proved as an important tools in studying receptors, ionchannels, and enzymes.

Many of these toxins are polypeptides (e.g. -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 ofnoveldrugs. For example, teprotide, a peptide isolated from the venom of the Brazilianviper, was the lead compound for the development of the antihypertensive agentscilazapril and captopril.

The neurotoxins from Clostridium botulinum are responsible for serious foodpoisoning (botulism), but they have a clinical use as well. They can be injected intospecific muscles (such as those controlling the eyelid) to prevent muscle spasm.These toxins prevent cholinergic transmission and could well prove a lead for thedevelopment of novel anticholinergic drugs.


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Natural cosmetic product

Natural cosmetics have become a major trend in recentyears 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 (ceyloncinnamon), Chamomile (babuna), Eucalyptus (bluegum), Grape seeds, Lavender oil, Lemon grass,Spearmint (mentha spicata), Mint arvensis, Nettleleaves, Neem tree, Patchouli oil, Rose petals, rosemary,Safflower,Walnut etc


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Consumers demand has led specialty retailers to expand

natural/organic products departments and increase their focus onthe category

40% of consumers currently use natural product at leastoccasionally, according to the market research firm, The HartmantGroup.

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

$9.3 billion and in 2005, organic sales alone are expected to reachnearly $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 Food and Beverage

Natural Products Research Report, Organic & Soy Sales Lead Category (2001). Michelle Moran.


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Natural dietary supplements

General public often considers botanical supplements

natural and safe alternatives to conventional syntheticpharmaceuticals

there is relatively little scientific evidence behind this believe..

Lot to be done to improve the efficacy, image and science behindbotanical dietary supplements.

Almost no sustained R&D efforts directed towards creating credible

product pipelines, quality control measures and discovery platformof this natural dietary supplements.


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Some of the dietary supplements sold in the market

Echinacea purpurea, L. angustifolia, DC. andpallida 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


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Supply of biomass

Biomass, a renewable energy source, is biological material derived fromliving, 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 orchemicals.

may also include biodegradable wastes that can be burnt as fuel.

Industrial biomass can be grown from numerous types of plants, includingmiscanthus, switchgrass, hemp, corn, poplar, willow, sorghum, sugarcane,and a variety oftree species, ranging from eucalyptus to oil palm (palm oil).

Research: Biomass conversion process to useful energy Chemical conversion

Biochemical conversion


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Specialty chemicalsAn area of study which malaysians have

not really considered in any great details

Potentially lucrative area in the era ofbiotechnological advancement

E.g. inhibitors, promoters in specific

reaction sequences etc.


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-THANK YOU-

Documents

Keynote B2 - Advances in Natural Product Research