The discovery of a new drug is part luck and part structured investigation. It originally started with drugs and lead compounds derived from natural sources, such as animals, plants, trees and microorganisms. Today, natural sources are still important, but the majority of lead compounds are synthesized in the laboratory. The nature of these synthetic compounds is initially decided from a consideration of the biochemistry of the pathogenic condition.
Today, many discoveries start with biological testing (bioassays or screening program) by pharmacologists of the potential sources in order to determine the nature of their pharmacological activity as well as their potencies. These screening programs may be random or focused. In random screening programs all the substances and compounds available are tested regardless of their structures. Random screening is still employed, but the use of more focused screening procedures where specific structural types are tested is now more common.
Once a screening program has identified substances of pharmacological activity of interest, the compound responsible for this activity is isolated and used as a lead compound for the production of related analogues. These compounds are subjected to further screening tests. This sequence of selective screening and synthesis of analogues may be repeated many times before a potentially useful drug is found.
Natural sources are still important sources of lead compounds and new drugs. However, the large diversity of potential natural sources in the world makes the technique of random screening a rather hit or miss process. The screening of local folk remedies (ethnopharmacology) offers the basis of a more systematic approach. In the past this has led to the discovery of many important therapeutic agents, for example, the antimalarial quinine from cinchona bark, the cardiac stimulant digitalis from fox gloves and the antihypertensive reserpine isolated from Rauwolfiaserpentina.
Once screening identifies a material containing an active compound, the problem becomes one of extraction, purification and assessment of the pharmacological activity. However, the isolation of useful quantities of a drug from its land or sea sources can cause ecological problems. The promising anticancer agent Taxol, for example, was originally isolated from the bark of the Pacific yew tree.
However, the production of large quantities of Taxol from this source would result in the wholesale destruction of the tree, a state of affairs that is ecologically unacceptable. It is vitally important that plant, shrub, tree and marine sources of the world are protected from further erosion, as there is no doubt that they will yield further useful therapeutic agents in the future.
The accidental discovery that some molds and other microorganisms produced substances – the so-called antibiotics – which were able to inhibit vital processes in higher organisms even in minute concentrations, led investigations, particularly after 1940, to an intensive search for new antibiotics. Today, antibiotics are searched for not only among microorganisms but also in plants and the higher animals. This investigation has resulted in the discovery, isolation, and identification of over 6000 antibiotics, of which, however, only about 100 are applied therapeutically.
On the other hand, thanks to the enormous progress of organic chemistry since the end of the nineteenth century, drugs of synthetic origin presently prevail in the therapeutic arsenal. Chemical synthesis has come to contribute more and more new drugs, chiefly after the growing application of knowledge of the mechanisms of chemical and biochemical reactions and the availability of efficient and rapid analytical methods, principally through chromatography, spectrophotometry, spectroscopy, and xray diffraction.
Side by side with products of microbial origin (principally, antibiotics and vitamins), new alkaloids, and those obtained totally by chemical synthesis, the therapeutic arsenal was also enriched by many semisynthetic drugs, introduced through chemical modification of vegetable, animal, or microbial products, such as alkaloids, hormones, and antibiotics, respectively.