Docking studies on a new human immunodeficiency virus integrase-Mg-DNA complex: phenyl ring exploration and synthesis of 1H-benzylindole derivatives through fluorine substitutions.
A new model of HIV-1 integrase-Mg-DNA complex that is useful for docking experiments has been built. It was used to study the binding mode of integrase strand transfer inhibitor 1 (CHI-1043) and other fluorine analogues. Molecular modeling results prompted us to synthesize the designed derivatives which showed potent enzymatic inhibition at nanomolar concentration, high antiviral activity, and low toxicity. Microwave assisted organic synthesis (MAOS) was employed in several steps of the synthetic pathway, thus reducing reaction times and improving yields.
Ferro
Stefania
S
Dipartimento Farmaco-Chimico, Universita di Messina, Viale Annunziata, 98168 Messina, Italy.
De Luca
Laura
L
Barreca
Maria Letizia
ML
Iraci
Nunzio
N
De Grazia
Sara
S
Christ
Frauke
F
Witvrouw
Myriam
M
Debyser
Zeger
Z
Chimirri
Alba
A
D002460:Cell Line; D004247:DNA / Q000737:chemistry*; D005461:Fluorine / Q000737:chemistry*; D019427:HIV Integrase / Q000737:chemistry*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry*; D008274:Magnesium / Q000737:chemistry*; D008958:Models, Molecular
D019428:HIV Integrase Inhibitors; D007211:Indoles; D005461:Fluorine; D004247:DNA; D019427:HIV Integrase; D008274:Magnesium