title: Indolylarylsulfones as HIV-1 non-nucleoside reverse transcriptase inhibitors: new cyclic substituents at indole-2-carboxamide.
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.
authors.affiliation: Istituto Pasteur - Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, Piazzale Aldo Moro 5, I-00185 Roma, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: La Regina
authors.forename: Antonio
authors.initials: A
authors.lastname: Coluccia
authors.forename: Andrea
authors.initials: A
authors.lastname: Brancale
authors.forename: Francesco
authors.initials: F
authors.lastname: Piscitelli
authors.forename: Valerio
authors.initials: V
authors.lastname: Gatti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Maga
authors.forename: Alberta
authors.initials: A
authors.lastname: Samuele
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.forename: Dominique
authors.initials: D
authors.lastname: Schols
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Romano
authors.initials: R
authors.lastname: Silvestri
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D048588:Benzoxazines / Q000494:pharmacology; D002478:Cells, Cultured; D003521:Cyclopropanes; D054303:HIV Reverse Transcriptase / Q000737:chemistry; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D008958:Models, Molecular; D008968:Molecular Conformation; D009154:Mutation; D019829:Nevirapine / Q000494:pharmacology; D009570:Nitriles; D011485:Protein Binding; D011724:Pyridazines / Q000494:pharmacology; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D007211:Indoles; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; D013450:Sulfones; C451734:etravirine; D019829:Nevirapine; D054303:HIV Reverse Transcriptase; C098320:efavirenz