Efficient 3D database screening for novel HIV-1 IN inhibitors.
We describe the use of pharmacophore modeling as an efficient tool in the discovery of novel HIV-1 integrase (IN) inhibitors. A three-dimensional hypothetical model for the binding of diketo acid analogues to the enzyme was built by means of the Catalyst program. Using these models as a query for virtual screening, we found several compounds that contain the specified 3D patterns of chemical functions. Biological testing shows that our strategy was successful in searching for new structural leads as HIV-1 IN inhibitors.
Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy. barreca@pharma.unime.it
Maria Letizia
ML
Barreca
Angela
A
Rao
Laura
L
De Luca
Maria
M
Zappalà
Cristina
C
Gurnari
Pietro
P
Monforte
Erik
E
De Clercq
Bénédicte
B
Van Maele
Zeger
Z
Debyser
Myriam
M
Witvrouw
James M
JM
Briggs
Alba
A
Chimirri
D003198:Computer Simulation; D004279:DNA, Viral / Q000187:drug effects / Q000235:genetics; D016208:Databases, Factual; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000706:statistics & numerical data*; D019428:HIV Integrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014584:User-Computer Interface
D004279:DNA, Viral; D019428:HIV Integrase Inhibitors