A simple, inexpensive apparatus for performance of preparative scale solution phase multiple parallel synthesis of drug analogs. II. Biological evaluation of a retrospective library of quinolone antiinfective agents.

Autor: Frank KE; Department of Medicinal Chemistry, Kansas University, Lawrence 66045-2506, USA., Devasthale PV, Gentry EJ, Ravikumar VT, Keschavarz-Shokri A, Mitscher LA, Nilius A, Shen LL, Shawar R, Baker WR
Jazyk: angličtina
Zdroj: Combinatorial chemistry & high throughput screening [Comb Chem High Throughput Screen] 1998 Jun; Vol. 1 (2), pp. 89-99.
Abstrakt: A series of pure fluoroquinolone antiinfective agents was prepared by multiple parallel synthesis using a simple new apparatus. These compounds were evaluated biologically against Gram-positive and Gram-negative microorganisms and against a BCG strain transfected with luciferase in a fluorescence-based antitubercular assay. Activity against relatively fast growing, acid-fast Mycobacterium smegmatis was determined in part by agar-dilution streak assays. Data obtained against Escherichia coli-derived DNA gyrase does not correlate well with whole cell assays against E. coli. These compounds were assayed by a convenient glass-fiber filter binding method modified for high throughput screening. In these analogs, the results with a N-1 cyclopropyl substituent were often inferior to those obtained with a N-1 2',4'-difluorophenyl substituent. None of the new compounds prepared was superior in its antimycobacterial potency to ciprofloxacin or temafloxacin.
Databáze: MEDLINE