Abstract
A novel series of trifluoromethyl indole derivatives have been designed, synthesized and evaluated for anti-HIV-1 activities in MT-2 cells. The hydrophobic constant, acute toxicity, carcinogenicity and mutagenicity were predicted. Trifluoromethyl indoles 10i and 10k showed extremely promising activities against WT HIV-1 with IC50 values at the low nanomolar level, similar to efavirenz, better than nevirapine, and also possessed higher potency towards the drug-resistant mutant strain Y181C than nevirapine. Preliminary SAR and docking studies of detailed binding mode provided some insights for discovery of more potent NNRTIs.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Aldehydes / chemistry
-
Alkynes
-
Benzoxazines / chemistry
-
Benzoxazines / pharmacology
-
Carcinogens / toxicity
-
Catalysis
-
Cell Line
-
Cyclopropanes
-
Drug Design*
-
Drug Resistance, Viral / drug effects*
-
HIV Reverse Transcriptase / chemistry
-
HIV Reverse Transcriptase / metabolism
-
HIV-1 / drug effects*
-
Humans
-
Indoles / chemical synthesis*
-
Indoles / chemistry
-
Indoles / pharmacology*
-
Ligands
-
Models, Molecular
-
Mutagens / toxicity
-
Mutant Proteins / chemistry
-
Mutant Proteins / metabolism
-
Reverse Transcriptase Inhibitors / chemical synthesis*
-
Reverse Transcriptase Inhibitors / chemistry
-
Reverse Transcriptase Inhibitors / pharmacology*
Substances
-
Aldehydes
-
Alkynes
-
Benzoxazines
-
Carcinogens
-
Cyclopropanes
-
Indoles
-
Ligands
-
Mutagens
-
Mutant Proteins
-
Reverse Transcriptase Inhibitors
-
3-hydroxybutanal
-
HIV Reverse Transcriptase
-
efavirenz