University of Zagazig, Egypt
Title: Role of natural compounds in drug discovery
Natural products are products from various natural sources, plants, microbes and animals. Natural products can be an entire organism (e.g. a plant, an animal or a micro- organism), a part of an organism (e.g. leaves or flowers of a plant, an isolated animal organ), an extract of an organism or part of an organism, or pure compound (e.g. alkaloids, coumarins, flavonoids, lignans, steroids and terpenoids) isolated from plants, animals or micro- organisms. ¢Nature has been a potential source of therapeutic agents for thousands of years. Over the last century, a number of top selling drugs have been developed from natural products. Example : ¢Anticancer drug Vincristine from Vinca rosea, narcotic analgesic Morphine from Papaver somniferum, antimalarial drug artemisinin from Artemisia annua, anticancer drug Taxol from Taxus brevifolia and antibiotic Penicillins from Penicillium ssp. are just a few examples.
In modern drug discovery and development processes, 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 could be an ideal drug candidate. There are at least 2,50,000 species of higher plants that exist on this planet, but merely five to 10 per cent have been investigated so far.
There are two ways of Drug discovery i) The Traditional way, ii) The Modern processes.
i) THE TRADITIONAL WAY, the extract 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. However, the process can be slow, inefficient and labor intensive.
ii) THE MODERN PROCESSES ¢ involve HTS, 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 of dereplicated natural products) needs to be built. Dereplication 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. LC-PDA (liquid chromatography–photo-diode- array detector), LC-MS (liquid chromatography–mass detector) and LC-NMR (liquid chromatography – nuclear magnetic resonance spectroscopy). 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 opportunity to handle the ‘lead’ rapidly for further developmental work.
To continue, the focus must be on exploiting newer approaches for natural product drug discovery e.g. the application of genomic tools, seeking novel sources of organisms from the environment, new screening technologies and improved processes of sample preparation for screening samples.