Title: HIV-1 integrase strand-transfer inhibitors: Design, synthesis and molecular modeling investigation
Authors: De Luca, Laura
De Grazia, Sara
Ferro, Stefania
Gitto, Rosaria
Christ, Frauke
Debyser, Zeger
Chimirri, Alba # ×
Issue Date: Feb-2011
Series Title: European Journal of Medicinal Chemistry vol:46 issue:2 pages:756-764
Abstract: This study is focused on a new series of benzylindole derivatives with various substituents at the benzene-fused ring, suggested by our 3D pharmacophore model developed for HIV-1 integrase inhibitors (INIs). All synthesized compounds proved to be active in the nanomolar range (6-35 nM) on the strand-transfer step (ST). In particular, derivative 4-[1-(4-fluorobenzyl)-5,7-dimethoxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acid (8e), presenting the highest best-fit value on pharmacophore model, showed a potency comparable to that of clinical INSTIs GS 9137 (1) and MK-0518 (2). The binding mode of our molecules has been investigated using the recently published crystal structure of the complex of full-length integrase from the prototype foamy virus in complex with its cognate DNA (PFV-IN/DNA). The results highlighted the ability of derivative 8e to assume the same binding mode of MK-0518 and GS 9137.
ISSN: 0223-5234
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Virology and Gene Therapy
× corresponding author
# (joint) last author

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