title: Computational strategies in discovering novel non-nucleoside inhibitors of HIV-1 RT.
abstract: A three-dimensional common feature pharmacophore model was developed using the X-ray structure of RT/non-nucleoside inhibitor (NNRTI) complexes. Starting from the pharmacophore hypothesis and the structure of the lead compound TBZ, new NNRTIs were designed and synthesized, having the benzimidazol-2-one system as a scaffold. Docking experiments showed that these molecules docked in a position and orientation similar to that of known inhibitors. Biological testing confirmed that our strategy was successful in searching for new leads as NNRTIs.
authors.affiliation: Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy. barreca@ pharma.unime.it
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Barreca
authors.forename: Angela
authors.initials: A
authors.lastname: Rao
authors.forename: Laura
authors.initials: L
authors.lastname: De Luca
authors.forename: Maria
authors.initials: M
authors.lastname: Zappalà
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Monforte
authors.forename: Giovanni
authors.initials: G
authors.lastname: Maga
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Alba
authors.initials: A
authors.lastname: Chimirri
authors.forename: Pietro
authors.initials: P
authors.lastname: Monforte
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D018360:Crystallography, X-Ray; D054303:HIV Reverse Transcriptase / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D001562:Benzimidazoles; D018894:Reverse Transcriptase Inhibitors; D013844:Thiazoles; D054303:HIV Reverse Transcriptase