PHARMACOGNOSY I LECTURES L.A. DILBREEN BARZANJI

Pharmacognosy Pharmacognosy may be defined as a branch of bioscience which treats in details medicinal and related products of crude matters obtained from plant, animal and mineral origins. In shorts, it is an objective study of crude drugs from natural sources treated scientifically and it encompasses the knowledge of the history, distribution, cultivation, collection, processing for market and preservation, the study of sensory, physical, chemical, and structural characteristic and the use of crude drugs.

Pharmacognosy also includes study of other materials used in pharmacy such as suspending, disintegrating and flavoring agent, filtering aids, etc. and substances like antibiotics, allergens, hallucinogenic and poisonous plants, immunizing agents, pesticides, raw materials for the production of oral contraceptives.

The word ‘Pharmacognosy’ had its debut in the early 19th century to designate the discipline related to medicinal plants; it is derived from the Greek pharmakon, ’a drug’, and gignosco, ‘to acquire knowledge of’. The term ‘Pharmacognosy’ was first coined by Johan Adam Schmidt (1759-1809) in his hand-written manuscript Lehrbuch der Materia Medica. Pharmacognosy is closely related to botany and plant chemistry and, indeed, both originated from the earlier scientific studies on medicinal plants.

The term ‘natural products’ used commonly in Pharmacognosy field; it refers to products from various natural sources, plants, microbes and animals. Natural products can be: an entire organism (e.g. a plant, an animal or a microorganism), a part of an organism ( e.g. leaves of a plant), an extract of organism or part of organism, pure compound (e.g. alkaloids, flavonoids, lignans, steroids, etc.) isolated from plants, animals or microorganism.

Over last century, a number of top selling drugs have been developed from natural products. Anticancer drug vincristine from Vinca rosea, narcotic analgesic morphine from Papaver somniferum, antimalarial drug artemisinin from Artemisia annua, anticancer drug Paclitaxil (Taxol ®) from Taxus brevifolia and antibiotic penicillin from Penicillium ssp.

A complete understanding of medicinal plants involves a number of disciplines including commerce, botany, horticulture, chemistry, enzymology, genetics, quality control pharmacology.

Pharmacognosists with a multidisciplinary background are able to make valuable contributions to these rapidly developing fields of study and pharmacists in general need to have a knowledge of, and to give professional advice on, the many herbal preparations available to public.

Drug discovery: Although drug discovery may be considered to be a recent concept that evolved from modern science during the 20th century, in reality the concept of drug discovery dates back many centuries, and has its origin in nature. In modern drug discovery and development process, natural products play an important role at the early stage of ‘lead’ discovery, i.e. discovery of the active natural molecule, which itself or its structural analogues can be an ideal drug candidate.

It is estimated that 61 % of 877 small molecule new chemical entities introduced as drugs worldwide during 1981-2002 can be traced back to or developed from natural products. These include : natural products 6%, natural product derivatives 27%, synthetic compounds with natural-product-derived pharmacophores 5%, synthetic compounds designed on the basis of knowledge gained from a natural product 23%.

Natural product drug discovery: the traditional way In the traditional, rather more academic, method of drug discovery from natural products, drug ragets are exposed to crude extracts, and in the case of a hit, i.e. any evidence of activity, the extract of is fractionated and the active compound is isolated and identified. Every step of fractionation and isolation is usually guided by bioassays, and the process is called bioassay guided isolation. The following scheme presents an overview of a bioassay-guided traditional natural product drug discovery process.

Source materials (e.g. plant) extract(s) active extract(s) Chromatographic fractionation Active fraction(s) chromatographic fractions Isolation and purification Isolated compounds active compound(s) Identification by spectroscopic techniques, e.g. UV , IR , MS ,NMR Identified compound(s) identified bioactive compound(s) extraction bioassay bioassay bioassay bioassay

Sometimes, a straight forward natural product isolation route, irrespective of bioactivity, is also applied, which results in the isolation of a number of natural compounds (small compound library) suitable for undergoing any bioactive screening. However, the process can be slow, inefficient and labour intensive, and it does not guarantee that a ‘lead’ from screening would be chemically workable or even patentable.

Natural product drug discovery: the modern process Modern drug discovery approaches involves HTS (high throughput screening), where, applying full automation and robotics, hundreds of molecules can be screened using several assays within a short time, and with very little amounts of compounds. In order to incorporate natural products in the modern HTS programmes, a natural product library (a collection dereplecated natural products) needs to be built. Dereplectaion is the process by which one can eliminate recurrence or re-isolation of same or similar compounds from various extracts.

A number of hyphenated techniques are used for dereplication, e. g A number of hyphenated techniques are used for dereplication, e.g. LC-PDA ( liquid chromatography-photo-diode-array detector), LC-MS (liquid chromatography-mass detector) and LC-NMR (liquid chromatography-nuclear magnetic resonance spectroscopy). While in the recent past it was extremely difficult, time consuming and labour intensive to build such a library from purified natural products, with the advent of newer and improved technologies related to separation, isolation and identification of natural products; the situation has improved remarkably.

Now, it is possible to build a ‘high quality’ and ‘chemically diverse’ natural product library that can be suitable for any modern HTS programmes. Natural product libraries can also be of crude extracts, chromatographic fractions or semi-purified compounds. However, the best result can be obtained from a fully identified pure natural product library as it provides scientists with the opportunities to handle the ‘lead’ rapidly for further developmental work, e.g. total or partial synthesis, dealing with formulation factors, in vivo assays and clinical trials.

Source materials (e.g. plant) extract(s) Chemical fingerprinting or dereplecation, e.g. use of LC-PDA, LC-MS, LC-NMR dereplicated extracts rapid isolation and purification e.g. HPLC Identification by spectroscopic techniques, e.g. UV , IR , MS ,NMR isolated compounds identified compounds (compound library) HTS Generation of ‘hit” Entry to the further developmental stages e.g. preformulation, formulation, in vivo assays, clinical trials, etc. Large-scale production of selected ‘hit’ compounds