Activity and molecular modeling of a new small molecule active against NNRTI-resistant HIV-1 mutants.
In this preliminary study we report the antiviral screening of triazolo[4,5-g]quinoline derivatives (compounds 1-6). 4,9-Dihydrotriazolo[4,5-g]quinoline-1-oxide (1) stood out as a new, small molecule endowed with a selective, promising activity in cell-based assays against HIV-1wt and clinically relevant NNRTI resistant mutants. In order to identify the molecular target, compound 1 was assayed in enzyme assay against the HIV-1wt RT. The molecular modeling strategy adopted yielded a rationale, in terms of molecular interactions and free energy of binding, for the possible reasons of the activity of this compound against NNRTI-resistant HIV-1 mutants with the RT isoforms K103N and Y181C.
Dipartimento Farmaco Chimico Tossicologico, Università di Sassari, Via Muroni 23/a, 07100 Sassari, Italy. acarta@uniss.it
Antonio
A
Carta
Sabrina
S
Pricl
Sandra
S
Piras
Maurizio
M
Fermeglia
Paolo
P
La Colla
Roberta
R
Loddo
D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D003497:Cyclic N-Oxides / Q000138:chemical synthesis* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024882:Drug Resistance, Viral / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D009154:Mutation; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013816:Thermodynamics
C547712:4,9-dihydrotriazolo(4,5-g)quinoline-1-oxide; D019380:Anti-HIV Agents; D003497:Cyclic N-Oxides; D011804:Quinolines; D018894:Reverse Transcriptase Inhibitors