title: 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.
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.
authors.affiliation: Department of Medicinal Chemistry, Kansas University, Lawrence 66045-2506, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Frank
authors.forename: P V
authors.initials: PV
authors.lastname: Devasthale
authors.forename: E J
authors.initials: EJ
authors.lastname: Gentry
authors.forename: V T
authors.initials: VT
authors.lastname: Ravikumar
authors.forename: A
authors.initials: A
authors.lastname: Keschavarz-Shokri
authors.forename: L A
authors.initials: LA
authors.lastname: Mitscher
authors.forename: A
authors.initials: A
authors.lastname: Nilius
authors.forename: L L
authors.initials: LL
authors.lastname: Shen
authors.forename: R
authors.initials: R
authors.lastname: Shawar
authors.forename: W R
authors.initials: WR
authors.lastname: Baker
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000295:instrumentation* / Q000379:methods; D004247:DNA / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000187:drug effects / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D024841:Fluoroquinolones; D008826:Microbial Sensitivity Tests; D009161:Mycobacterium / Q000187:drug effects; D015363:Quinolones / Q000494:pharmacology; D012016:Reference Values; D012996:Solutions / Q000737:chemistry*; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
chemical_list: D000890:Anti-Infective Agents; D004791:Enzyme Inhibitors; D024841:Fluoroquinolones; D015363:Quinolones; D012996:Solutions; D059005:Topoisomerase II Inhibitors; C054745:temafloxacin; D004247:DNA; D004250:DNA Topoisomerases, Type II