1. PLANT SOURCES:

Plants have always been a rich source of lead compounds (e.g. morphine, cocaine, digitalis, quinine, tubocurarine, nicotine, 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). 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.
Plants provide a large bank of rich, complex and highly varied structures which are unlikely to be synthesized in laboratories. Furthermore, evolution has already carried out a screening process itself whereby plants are more likely to survive if they contain potent compounds which deter animals or insects from eating them. Even today, the number of plants that have been extensively studied is relatively very few and the vast majority has not been studied at all.

2. ANIMAL SOURCES:

Animals can sometimes be a source of new lead compounds. For example, 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.

3. MARINE SOURCES:

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.
Natural products from marine organisms are released into the water and therefore are rapidly diluted; accordingly they must be very potent materials to have the desired end effect. The richly available marine biodiversity that is available to us has to this point only been explored to an extremely limited extent. Furthermore, the primary chemical diversity available from marine organisms is most likely capable of delivering an even greater abundance of secondary metabolites for research use. For all of these reasons it is believed that the natural products that are available from the seas and oceans provide a tremendous opportunity for the discovery of novel therapeutic agents. The first discovery of a marine-based biologically active compound of therapeutic interest was really quite by accident approximately 10 years after the end of the World War II [29, 30]. The C-nucleosides isolated from the Caribbean sponge Cryptotheca crypta were found to possess antiviral activity.  

This discovery eventually led to the development of cytosine arabinoside, a useful antineoplastic agent. Biologically active marine proteins derived from the venom of marine snails of the Conus genus have attracted a significant level of research over the years. These conotoxin peptides interact in a unique fashion with voltage-gated ion channels to induce a wide spectrum of Pharmacological effects. Such effects include anesthesia, analgesia, and anticonvulsant activity. The conotoxin ziconotide is currently under review in the United States for use in the treatment of chronic, opiate-resistant pain.
According to some estimates, there are most likely approximately 1000 different Conus snails. Each snail produces up to approximately 200 different venoms. The broad spectrum of biological activities manifested by each of these venom components multiplied by the number of snails and venom components available suggests significant opportunity for new drugs from the snail alone. The mussel Mytilis edulis has been reported to produce antibacterial peptides and cytotoxic lectins. Horseshoe crabs produce a variety of different antibacterial peptides and proteins. Indeed, Limulus polyphemus produces an interesting group of antimicrobial peptides referred to as polyphemusins, and a synthetic peptide based on the sequence of polyphemusin II has been reported to strongly inhibit the cytopathic effect of infection with HIV.

4. MICROBIAL SOURCES:

Microorganisms such as bacteria and fungi have been invaluable for discovering drugs and lead compounds. These microorganisms 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. Soil and water samples were collected from all over the world in order to study new bacterial or fungal strains, leading to an impressive arsenal of antibacterial agents such as the cephalosporins, tetracyclines, aminoglycosides, rifamycins, and chloramphenicol.
Although most of the drugs derived from microorganisms are used in antibacterial therapy, some microbial metabolites have provided lead compounds in other fields of medicine. For example, 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 also 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. Other examples include the fungal metabolite lovastatin, which was the lead compound for a series of drugs that lower cholesterol levels, and another fungal metabolite called ciclosporin which is used to suppress the immune response after transplantation operations.
Microorganisms have proven to be an excellent source of novel natural products including polyketide and peptide antibiotics as well as classes of other biologically active compounds. Today, microbial metabolites are used as antineoplastic agents (e.g., mitomycin), immunosuppressive agents (e.g., rapamycin), hypocholesterolemic agents (e.g., pravastatin), enzyme inhibitors (e.g., desferal), antimigraine agents (e.g., ergot alkaloids), herbicides (e.g., bialaphos), antiparasitic agents (e.g., salinomycin), bioinsecticides (e.g., tetranactin), and ruminant growth promoters (e.g., monensin). It is noteworthy that some of these compounds when originally discovered failed in their development for their original uses as either antibiotics or as agricultural fungicides. Bacteriocins are ribosomally produced antibiotic peptides and proteins that can be subdivided into different categories, antibiotics, and microcins. Lantibiotics are produced by Gram-positive bacteria and microcins are produced by Gram-negative bacteria. Both antibiotics and microcins possess an ability to form pores or punch holes in membranes of susceptible microorganisms. This property is of interest to the food industry, as bacteriocins are produced by Lactococcus spp., which are used in the preservation of various foodstuffs.