Design of β-Lactams with Mechanism Based Nonantibacterial Activities
Authors: Veinberg, Grigory; Vorona, Maxim; Shestakova, Irina; Kanepe, Iveta; Lukevics, Edmunds
Source: Current Medicinal Chemistry, Volume 10, Number 17, September 2003 , pp. 1741-1757(17)
Publisher: Bentham Science Publishers
Abstract:The majority of nonantibacterial activities discovered for β-lactam derivatives during the last 15 years are based on their ability to form a stable covalent complex with nucleophile in the active site of enzymes regulating fundamental physiological processes in mammalian organism such as serine and cysteine proteases, LDL phospholipase A2, A-independent transacylase and some still indeciphered enzymes. Regulation of their catalytic activity both in vitro and in vivo by compounds designed on the cephalosporin, penicillin and 2-azetidinone base was successfully exploited in the treatment of inflammatory, respiratory, cardiovascular disorders, cancer and other pathologic processes. Availability of X-ray crystallographic data for target enzymes and computational molecular modelling in combination with wide possibilities of structural modifications for commercial natural and synthetic β-lactams and the chiral blocks allow to consider this class of organic compounds as a perspective source of mechanism based nonantibacterial drugs.
Document Type: Review Article
Affiliations: Latvian Institute of Organic Synthesis, 21 Aizkraukles Street, Riga, LV 1006, Latvia.
Publication date: September 2003
- Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.