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

Comb Chem High Throughput Screen. 1998 Jun;1(2):89-99.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-Infective Agents / chemical synthesis*
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacology*
  • Chemistry, Pharmaceutical / instrumentation*
  • Chemistry, Pharmaceutical / methods
  • DNA / metabolism
  • DNA Topoisomerases, Type II / drug effects
  • DNA Topoisomerases, Type II / metabolism
  • Drug Evaluation, Preclinical / methods*
  • Enzyme Inhibitors / pharmacology
  • Fluoroquinolones*
  • Microbial Sensitivity Tests
  • Mycobacterium / drug effects
  • Quinolones / pharmacology
  • Reference Values
  • Solutions / chemistry*
  • Structure-Activity Relationship
  • Topoisomerase II Inhibitors

Substances

  • Anti-Infective Agents
  • Enzyme Inhibitors
  • Fluoroquinolones
  • Quinolones
  • Solutions
  • Topoisomerase II Inhibitors
  • temafloxacin
  • DNA
  • DNA Topoisomerases, Type II