title: Chromone and chromanone derivatives as strand transfer inhibitors of HIV-1 integrase.
abstract: HIV-1 integrase catalyzes terminal cleavage at the 3' end of the proviral DNA, removing a pair of bases and causing strand transfer by joining the 3' end to 5'-phosphates in the target DNA. Several aryl 1,3-diketo acids that can inhibit the strand transfer reaction of HIV-1 IN have been identified. Here we synthesized a new series of compounds with a chromone or chromanone ring as conformationally constrained scaffolds of 1,3-diketo acids, and then tested their ability to inhibit HIV-1 IN-mediated strand transfer. All compounds moderately inhibited HIV-1 IN activity, indicating that the conformational restriction of one keto group into a chromone or chromanone ring decreases inhibition of the HIV-1 IN strand transfer.
authors.affiliation: Division of Life Sciences, Korea Institute of Science & Technology, Seoul 130-650, Korea.
authors.forename: Jang Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Seung Uk
authors.initials: SU
authors.lastname: Lee
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Seo Yeong
authors.initials: SY
authors.lastname: Shin
authors.forename: Jae Yeol
authors.initials: JY
authors.lastname: Lee
authors.forename: Cha-Gyun
authors.initials: CG
authors.lastname: Shin
authors.forename: Kyung Ho
authors.initials: KH
authors.lastname: Yoo
authors.forename: Yong Sup
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000880:Anthraquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002867:Chromones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004279:DNA, Viral / Q000187:drug effects; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D006860:Hydrogen Bonding; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation
chemical_list: D000880:Anthraquinones; D002867:Chromones; D004279:DNA, Viral; D019428:HIV Integrase Inhibitors; D007202:Indicators and Reagents; C469373:chaetomanone