title: Novel screen methodologies for identification of new microbial metabolites with pharmacological activity.
abstract: Micro-organisms continue to provide an important source of chemical diversity for the discovery of compounds with new biological activities. Microbial metabolites discovered recently using assays to detect compounds with potential pharmacological utility are surveyed and found to represent an extensive range of structural types produced by a wide variety of organisms. Assays used for screening samples produced by microbial processes must be robust, sensitive and specific and able to operate above a background of potential interferences from a number of sources. Discovery assays currently in use fall into three main categories cell-based, receptor-ligand interaction and enzyme inhibition assays. Trends in the use of these assays and new developments in assay technology applicable to the screening of microbial samples are examined with particular reference to the high throughput screening environment. For microbial screening to be a competitive route to new drug leads, the disciplines involved must be engineered into a seamlessly integrated process to deliver novel compounds with the required biological properties rapidly.
authors.affiliation: Xenova Ltd, Berkshire, UK.
authors.forename: D C
authors.initials: DC
authors.lastname: Hill
authors.forename: S K
authors.initials: SK
authors.lastname: Wrigley
authors.forename: L J
authors.initials: LJ
authors.lastname: Nisbet
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000302:isolation & purification / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000188:drug therapy; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006168:Guinea Pigs; D006801:Humans; D007218:Industrial Microbiology / Q000379:methods*; D007249:Inflammation / Q000188:drug therapy; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D009414:Nerve Growth Factors / Q000138:chemical synthesis / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D011955:Receptors, Drug / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D002317:Cardiovascular Agents; D009414:Nerve Growth Factors; D010975:Platelet Aggregation Inhibitors; D011955:Receptors, Drug