title: Development of a series of 3-hydroxyquinolin-2(1H)-ones as selective inhibitors of HIV-1 reverse transcriptase associated RNase H activity.
abstract: We report herein the synthesis of a series of 3-hydroxyquinolin-2(1H)-one derivatives. Esters and amide groups were introduced at position 4 of the basis scaffold and some modulations of the benzenic moiety were performed. Most compounds presented selective inhibitory properties in the 10-20 μM range against HIV-1 reverse transcriptase associated ribonuclease H activity, without affecting the integrase and reverse transcriptase DNA polymerase activities. Unfortunately all tested compounds exhibited high cellular cytotoxicity in cell culture which limited their applications as antiviral agents.
authors.affiliation: Université Lille Nord de France, F-59000 Lille, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Suchaud
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bailly
authors.forename: Cédric
authors.initials: C
authors.lastname: Lion
authors.forename: Enzo
authors.initials: E
authors.lastname: Tramontano
authors.forename: Francesca
authors.initials: F
authors.lastname: Esposito
authors.forename: Angela
authors.initials: A
authors.lastname: Corona
authors.forename: Frauke
authors.initials: F
authors.lastname: Christ
authors.forename: Zeger
authors.initials: Z
authors.lastname: Debyser
authors.forename: Philippe
authors.initials: P
authors.lastname: Cotelle
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005453:Fluorescence; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D008274:Magnesium / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D054309:Ribonuclease H, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D015363:Quinolones; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D054309:Ribonuclease H, Human Immunodeficiency Virus; D008274:Magnesium