Abstract
New indolylarylsulfone derivatives bearing cyclic substituents at indole-2-carboxamide linked through a methylene/ethylene spacer were potent inhibitors of the WT HIV-1 replication in CEM and PBMC cells with inhibitory concentrations in the low nanomolar range. Against the mutant L100I and K103N RT HIV-1 strains in MT-4 cells, compounds 20, 24-26, 36, and 40 showed antiviral potency superior to that of NVP and EFV. Against these mutant strains, derivatives 20, 24-26, and 40 were equipotent to ETV. Molecular docking experiments on this novel series of IAS analogues have also suggested that the H-bond interaction between the nitrogen atom in the carboxamide chain of IAS and Glu138:B is important in the binding of these compounds. These results are in accordance with the experimental data obtained on the WT and on the mutant HIV-1 strains tested.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkynes
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Anti-HIV Agents / chemical synthesis*
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Anti-HIV Agents / chemistry
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Anti-HIV Agents / pharmacology
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Benzoxazines / pharmacology
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Cells, Cultured
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Cyclopropanes
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HIV Reverse Transcriptase / chemistry
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HIV-1 / drug effects*
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HIV-1 / genetics
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Humans
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Indoles / chemical synthesis*
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Indoles / chemistry
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Indoles / pharmacology
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Leukocytes, Mononuclear / drug effects
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Leukocytes, Mononuclear / virology
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Models, Molecular
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Molecular Conformation
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Mutation
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Nevirapine / pharmacology
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Nitriles
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Protein Binding
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Pyridazines / pharmacology
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Pyrimidines
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Reverse Transcriptase Inhibitors / chemical synthesis*
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Reverse Transcriptase Inhibitors / chemistry
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Reverse Transcriptase Inhibitors / pharmacology
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Structure-Activity Relationship
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Sulfones / chemical synthesis*
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Sulfones / chemistry
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Sulfones / pharmacology
Substances
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Alkynes
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Anti-HIV Agents
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Benzoxazines
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Cyclopropanes
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Indoles
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Nitriles
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Pyridazines
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Pyrimidines
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Reverse Transcriptase Inhibitors
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Sulfones
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etravirine
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Nevirapine
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HIV Reverse Transcriptase
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efavirenz