title: Indolyl aryl sulfones as HIV-1 non-nucleoside reverse transcriptase inhibitors: role of two halogen atoms at the indole ring in developing new analogues with improved antiviral activity.
abstract: Indolyl aryl sulfones bearing the 4,5-difluoro (10) or 5-chloro-4-fluoro (16) substitution pattern at the indole ring were potent inhibitors of HIV-1 WT and the NNRTI-resistant strains Y181C and K103N-Y181C. These compounds were highly effective against the 112 and the AB1 strains in lymphocytes and inhibited at nanomolar concentration the multiplication of the IIIBBa-L strain in macrophages. Compound 16 was exceptionally potent against RT WT and RTs carrying the K103N, Y181I, and L100I mutations.
authors.affiliation: Istituto Pasteur--Fondazione Cenci Bolognetti, Dipartimento di Studi Farmaceutici, Sapienza Università di Roma, Piazzale Aldo Moro 5, I-00185 Roma, Italy.
authors.forename: Giuseppe La
authors.initials: GL
authors.lastname: Regina
authors.forename: Antonio
authors.initials: A
authors.lastname: Coluccia
authors.forename: Francesco
authors.initials: F
authors.lastname: Piscitelli
authors.forename: Alberto
authors.initials: A
authors.lastname: Bergamini
authors.forename: Anna
authors.initials: A
authors.lastname: Sinistro
authors.forename: Antonella
authors.initials: A
authors.lastname: Cavazza
authors.forename: Giovanni
authors.initials: G
authors.lastname: Maga
authors.forename: Alberta
authors.initials: A
authors.lastname: Samuele
authors.forename: Samantha
authors.initials: S
authors.lastname: Zanoli
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Marino
authors.initials: M
authors.lastname: Artico
authors.forename: Romano
authors.initials: R
authors.lastname: Silvestri
mesh_terms: D002460:Cell Line; D024882:Drug Resistance, Viral; D054303:HIV Reverse Transcriptase / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000821:virology; D008264:Macrophages / Q000187:drug effects / Q000821:virology; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology