title: Development and in Vitro Evaluation of a Microbicide Gel Formulation for a Novel Non-Nucleoside Reverse Transcriptase Inhibitor Belonging to the N-Dihydroalkyloxybenzyloxopyrimidines (N-DABOs) Family.
abstract: Preventing HIV transmission by the use of a vaginal microbicide is a topic of considerable interest in the fight against AIDS. Both a potent anti-HIV agent and an efficient formulation are required to develop a successful microbicide. In this regard, molecules able to inhibit the HIV replication before the integration of the viral DNA into the genetic material of the host cells, such as entry inhibitors or reverse transcriptase inhibitors (RTIs), are ideal candidates for prevention purpose. Among RTIs, S- and N-dihydroalkyloxybenzyloxopyrimidines (S-DABOs and N-DABOs) are interesting compounds active at nanomolar concentration against wild type of RT and with a very interesting activity against RT mutations. Herein, novel N-DABOs were synthesized and tested as anti-HIV agents. Furthermore, their mode of binding was studied by molecular modeling. At the same time, a vaginal microbicide gel formulation was developed and tested for one of the most promising candidates.
authors.affiliation: Dipartimento Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena , Via A. De Gasperi 2, I-53100 Siena, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Tintori
authors.affiliation: Dipartimento Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena , Via A. De Gasperi 2, I-53100 Siena, Italy.
authors.forename: Annalaura
authors.initials: A
authors.lastname: Brai
authors.affiliation: Dipartimento Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena , Via A. De Gasperi 2, I-53100 Siena, Italy.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Dasso Lang
authors.affiliation: Dipartimento Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena , Via A. De Gasperi 2, I-53100 Siena, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Deodato
authors.affiliation: Dipartimento Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena , Via A. De Gasperi 2, I-53100 Siena, Italy.
authors.forename: Antonia Michela
authors.initials: AM
authors.lastname: Greco
authors.affiliation: Dipartimento Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena , Via A. De Gasperi 2, I-53100 Siena, Italy.
authors.forename: Bruno Mattia
authors.initials: BM
authors.lastname: Bizzarri
authors.affiliation: Dipartimento Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena , Via A. De Gasperi 2, I-53100 Siena, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Cascone
authors.affiliation: Dipartimento Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena , Via A. De Gasperi 2, I-53100 Siena, Italy.
authors.forename: Alexandru
authors.initials: A
authors.lastname: Casian
authors.affiliation: Dipartimento Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena , Via A. De Gasperi 2, I-53100 Siena, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Zamperini
authors.affiliation: Dipartimento Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena , Via A. De Gasperi 2, I-53100 Siena, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Dreassi
authors.affiliation: Istituto di Genetica Molecolare, IGM-CNR, Via Abbiategrasso 207, I-27100 Pavia, Italy.
authors.forename: Emmanuele
authors.initials: E
authors.lastname: Crespan
authors.affiliation: Istituto di Genetica Molecolare, IGM-CNR, Via Abbiategrasso 207, I-27100 Pavia, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Maga
authors.affiliation: Virology Unit, Institute of Tropical Medicine , Nationalestraat 155, B-2000 Antwerpen, Belgium.
authors.forename: Guido
authors.initials: G
authors.lastname: Vanham
authors.affiliation: Department of Biotechnology and Life Sciences, University of Insubria , Dunant 3, 21100, Varese, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Ceresola
authors.affiliation: Department of Biotechnology and Life Sciences, University of Insubria , Dunant 3, 21100, Varese, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Canducci
authors.affiliation: Virology Unit, Institute of Tropical Medicine , Nationalestraat 155, B-2000 Antwerpen, Belgium.
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Ariën
authors.affiliation: Dipartimento Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena , Via A. De Gasperi 2, I-53100 Siena, Italy.|Biotechnology College of Science and Technology, Temple University , Biolife Science Building, Suite 333, 1900 N 12th Street, Philadelphia, Pennsylvania 19122, United States.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Botta
mesh_terms: D000282:Administration, Intravaginal; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004279:DNA, Viral / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005782:Gels; D015497:HIV-1 / Q000187:drug effects; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D005782:Gels; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors