Pharmacognosy and Drug Discovery

Prof. Suleiman Olimat

The World Health Organization (WHO) estimated that as much as 80 per cent of the world’s population relies on traditional forms of medicine, chiefly plants .More than 80,0000 of the 250,000 species of flowering plants of the world have been documented to be used in various human cultures around the world for medicinal purposes . However, the number could be higher as knowledge on the indigenous uses of plants as medicines was mostly passed on orally from one generation to another and has largely remained undocumented. Some of the traditional knowledge might be lost as some practitioners were secretive and reluctant to reveal enough information .

The Role of Plant-Derived Compoundsin Drug Development

Despite the recent interest in drug discovery by molecular modeling, combinatorial chemistry, and other synthetic chemistry methods, natural-product-derived compounds are still proving to be an invaluable source of medicines for humans. Other than the direct usage of plant secondarymetabolites in their original forms as drugs, these compounds can also be used as drug precursors, templates for synthetic modification, and pharmacological probes.

Types of drugs derived from plants

1. Herbal drugs, derived from specific parts of a

medicinal plant

2. Compounds isolated from nature

3. Nutraceuticals, or “functional foods”

IV. The role of natural products in drug discovery

1. Combinatorial chemistry

2. High-throughput screening of natural products

3. Combinatorial biosynthesis

4. Ethnopharmacology

V. General principles of botany: morphology and systematics

• How to define a pharmaceutical plant-derived drug from the botanical point of view ?

a botanical drug is a product that is either:

Derived from a plant and transformed into a drug by drying certain plant parts, or sometimes the whole plant, or

1. Obtained from a plant, but no longer retains the structure of the plant or its organs and contains a complex mixture of biogenic compounds (e.g. fatty and essential oils, gums, resins, balms)

•isolated pure natural products are thus not “botanical drugs”, but rather chemically defined

drugs derived from nature.

the following plant organs are the most important, with the Latin name that is used, for example in international trade, in parentheses:

1. Aerial parts or herb (herba)2. Leaf (folia)3. Flower (flos)4. Fruit (fructus)5. Bark (cortex)6. Root (radix)7. Rhizome (rhizoma)8. Bulb (bulbus)

Three New Nobel Prize

Scientists deal with Pharmacognosy and Natural Products Chemistry), congratulate three scientists whose work in pharmacognosy, the study of natural compounds, led to being awarded the 2015 Nobel Prize this year.

The 2015 Nobel Prize in Physiology or Medicine winners Drs. William C. Campbell, Satoshi Ōmura and Youyou Tu were honored for the discovery of novel natural products that became impactful therapies for infections by roundworm parasites and malaria.

William C. Campbell and Satoshi Ōmura

Dr. Ōmura was honored by the Nobel committee jointly with Dr. Campbell, previously at the Merck Institute for Therapeutic Research, where he showed that Avermectin was active against the roundworm parasites. Avermectin and its analog Ivermectin, created by Dr. Campbell and colleagues, are now the standard of care for these infections in both humans and animals and have dramatically reduced the human suffering from river blindness and elephantitis. Due to the effects of Avermectin and its analogs, these diseases are on the verge of eradication.

AvermectinsThe avermectins are a series 16-membered macrocyclic lactone derivatives with potent anthelmintic and insecticidal properties. These naturally occurring compounds are generated as fermentation products byStreptomyces avermitilis, a soil actinomycete. Eight different avermectins were isolated in 4 pairs of homologue compounds, with a major (a-component) and minor (b-component) component usually in ratios of 80:20 to 90:10. Other anthelmintics derived from the avermectins include ivermectin, selamectin, doramectin andabamectin.

Ivermectin

Ivermectin (22,23-dihydroavermectin B1a + 22,23-dihydroavermectin B1b) is a broad-spectrum antiparasitic drugin the avermectin family.

Uses

Ivermectin is a broad-spectrum antiparasitic agent, traditionally against parasitic worms. It is mainly used in humans in the treatment of onchocerciasis (river blindness), but is also effective against other worm infestations (such as as strongyloidiasis, ascariasis, trichuriasis, filariasis and enterobiasis), and some epidermal parasitic skin diseases, including scabies.The drug rapidly kills microfilariae, but not the adult worms. An Ivermectin cream has been approved by the FDA for treatment of rosacea.

Dr. Youyou Tu

Dr. Tu has been honored for her discovery of the antimalarial compound artemisinin, which she isolated from the plant Artemisia annua (Asteraceae). Artemisia annua, also known as sweet wormwood or qīnghāo, is a plant that had been used in traditional Chinese herbal medicines, for fevers from infection.

Artemisia annua

Artemisinin

Artemisinin proved a spectacularly effective drug against malaria by rapidly killing Plasmodium parasites at an early stage in their development. Artemisinin, is part of current combination therapy for malaria that has been reported to reduce the mortality from this parasite by 20-30%, saving hundreds of thousands of lives per year.

Artemisinin

Taxus brevifolia

(Taxol)

Plant Secondary Metabolites as Drug Precursors

Some natural products obtained from plants can be used as small-molecule drug precursors, which can be converted into the compound of interest by chemical modification or fermentation methods. The semisynthetic approach is usually used to resolve the shortage of supply due to the low yield of compounds fromplants and/or the high cost of total synthesis. For compounds with complex structures and many chiral centers, protracted methods may be needed for their synthesis, and thus these methods would not be feasible economically. The following examples indicate that some secondary metabolites from plants are useful drug precursors, although they are not necessarily pharmacologically active in their original naturally occurring forms.

Cropping of the bark of the slow-growing Pacific yew tree, Taxus brevifolia Nutt., is not a feasible method to provide sufficient amounts of the antitumor drug paclitaxel (1, Taxol) to meet the market demand (paclitaxel was originally isolated in only 0.014 % w/w yield from the bark of Taxus brevifolia) . Even though this compound can be produced by total synthesis, this has proven tobe inefficient in affording large quantities of paclitaxel . Fortunately,10-deacetylbaccatin III (2) can be isolated in relatively large amounts from the needles of other related yew species, such as Taxus baccata L. (a renewable resource), and can be converted chemically in several steps into paclitaxel .During the period 1993–2002, the main pharmaceutical manufacturer, Bristol-Myers Squibb, adopted the semisynthetic method to produce paclitaxel from 10-deacetylbaccatin III . Since2002, Bristol-Myers Squibb has produced paclitaxel using a plant cell culture method.

Dioscorea species

Diosgenin , a steroidal sapogenin obtained from the tubers of variousDioscorea species that grow in Mexico and Central America, can be convertedchemically in several steps into progesterone , a hormone that can be used as a female oral contraceptive . Originally, progesterone was isolated from sow ovaries with a very low yield (20 mg from 625 kg of ovaries), and later was synthesized from cholesterol with very low efficiency . Progesterone is also a key intermediate for the production of cortisone , an important anti-inflammatory drug. Progesterone can be converted into 11α-hydroxyprogesterone by microbial hydroxylation at C-11, followed by chemical reactions, to produce cortisone . Until now, diosgenin is still an important starting material for the production of various steroid hormones.

Diosgenin

Progesterone from Diosgenin

(Illicium verum)Star Anise

Oseltamivir phosphate ( Tamiflu)Oseltamivir phosphate (7, Tamiflu) is an orally active neuraminidase inhibitordeveloped for the treatment and prophylaxis of influenza viruses A and B[34, 35]. The starting material for the oseltamivir synthesis is (−)-shikimic acid(8), an important biochemical intermediate in plants and microorganisms [36].Previously, shikimic acid was extracted solely from the fruits of the shikimitree (Illicium verum Hook.f.), also known as star anise, which contains a largeamount of this compound . Later on, shikimic acid was obtained from thefermentation of genetically engineered Escherichia coli strains, which are deficientin the shikimate kinase gene . Currently, Roche, the drug manufacturer,still relies on both extraction and fermentation methods to obtain tonquantities of shikimic acid . Several routes for the production of oseltamivirindependent of shikimic acid have been developed , but these alternativesare still not cost efficient .

Galega officinalis L.

Guanidine is a natural product with good hypoglycemic activity isolated from Galega officinalis L., but is too toxic for clinical use . Many derivatives of guanidine have been synthesized, and metformin (dimethylbiguanide) was later found to be clinically suitable for treatment of type II diabetes .

Guanidine and Metformin

Gila Monster (Heloderma suspectum)

Have you ever seen a pink yellow lizard? You were probably looking at a Gila Monster. Did you no it’s poisonous? Gila Monsters are cool, or at least that’s only what I think. You will find the habitat, physical description, its diet, and its life cycle very interesting.

Physical description

The Gila Monster is very interesting when it comes to the physical description. Gila Monster has a fat tail. It also has bony scales. Also the Gila Monster is 56 centimeters long. The Gila Monsters appearance is very attractive

Life Cycle

When The Gila Monster hatches it starts its life cycle like other lizards. Did you know The Gila Monster is hatched? The Gila Monster can live an average of 25 years. It takes it two years for it to grow from baby to adult. The Gila Monster lives a long life.

Exenatide

• Exenatide, a drug that is a synthetic form of a substance found in Gila monster saliva, led to healthy sustained glucose levels and progressive weight loss among people .

• Exenatide, marketed as Byetta, was approved by the Food and Drug Administration in April 2005 to treat type 2 diabetes in patients who were not able to get their high blood sugar under control in a combination with one or more of three other medications, metformin or sulfonylurea thiazolidinedione.