Chromone and chromanone derivatives as strand transfer inhibitors of HIV-1 integrase.
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.
Park
Jang Hyun
JH
Division of Life Sciences, Korea Institute of Science & Technology, Seoul 130-650, Korea.
Lee
Seung Uk
SU
Kim
Sang Hoon
SH
Shin
Seo Yeong
SY
Lee
Jae Yeol
JY
Shin
Cha-Gyun
CG
Yoo
Kyung Ho
KH
Lee
Yong Sup
YS
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
D000880:Anthraquinones; D002867:Chromones; D004279:DNA, Viral; D019428:HIV Integrase Inhibitors; D007202:Indicators and Reagents; C469373:chaetomanone