Pharmacophore-based design of HIV-1 integrase strand-transfer inhibitors.
Using a training set of diketo-like acid HIV-1 integrase (IN) strand-transfer inhibitors, a 3D pharmacophore model was derived having quantitative predictive ability in terms of activity. The best statistical hypothesis consisted of four features (one hydrophobic aromatic region, two hydrogen-bond acceptors, and one hydrogen-bond donor) with r of 0.96. The resulting pharmacophore model guided the rational design of benzylindoles as new potent IN inhibitors, whose microwave-assisted synthesis and biological evaluation are reported.
Barreca
Maria Letizia
ML
Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy. barreca@pharma.unime.it
Ferro
Stefania
S
Rao
Angela
A
De Luca
Laura
L
Zappalà
Maria
M
Monforte
Anna-Maria
AM
Debyser
Zeger
Z
Witvrouw
Myriam
M
Chimirri
Alba
A
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D015195:Drug Design; D019427:HIV Integrase / Q000737:chemistry*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007651:Keto Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000821:virology; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship
D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; D007651:Keto Acids; D019427:HIV Integrase