74
D.C. Hill et al.
4.3 Cardiovascular Disease ....................................
103
4.3.1 Inhibition of Cholesterol Metabolism ........................
103
4.3.2 Smooth Muscle Contraction Inhihitors .......................
106
4.3.3 Inhibition of Plasminogen Activator Inhibitor-I ..................
106
4.4 CNS Disease ..........................................
107
4.4.1 General Screen Methodologies and Targets .....................
107
5 Discussion and Conclusions ....................................
107
5.1 Review of Compounds Identified ..............................
107
5.2 Review of Screen Methodologies ..............................
108
5.3 Developments in Assay Technology for New Drug Discovery .............
109
5.4 Rapid Delivery of New Drug Leads from Natural Products Sources .........
115
6 References ..............................................
116
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
curently 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.
D.C. Hill et al.
4.3 Cardiovascular Disease ....................................
103
4.3.1 Inhibition of Cholesterol Metabolism ........................
103
4.3.2 Smooth Muscle Contraction Inhihitors .......................
106
4.3.3 Inhibition of Plasminogen Activator Inhibitor-I ..................
106
4.4 CNS Disease ..........................................
107
4.4.1 General Screen Methodologies and Targets .....................
107
5 Discussion and Conclusions ....................................
107
5.1 Review of Compounds Identified ..............................
107
5.2 Review of Screen Methodologies ..............................
108
5.3 Developments in Assay Technology for New Drug Discovery .............
109
5.4 Rapid Delivery of New Drug Leads from Natural Products Sources .........
115
6 References ..............................................
116
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
curently 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.