title: 2-Aminothiazolones as anti-HIV agents that act as gp120-CD4 inhibitors.
abstract: We report here the synthesis of 2-aminothiazolones along with their biological properties as novel anti-HIV agents. Such compounds have proven to act through the inhibition of the gp120-CD4 protein-protein interaction that occurs at the very early stage of the HIV-1 entry process. No cytotoxicity was found for these compounds, and broad antiviral activities against laboratory strains and pseudotyped viruses were documented. Docking simulations have also been applied to predict the mechanism, at the molecular level, by which the inhibitors were able to interact within the Phe43 cavity of HIV-1 gp120. Furthermore, a preliminary absorption, distribution, metabolism, and excretion (ADME) evaluation was performed. Overall, this study led the basis for the development of more potent HIV entry inhibitors.
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Siena, Italy.
authors.forename: Marika
authors.initials: M
authors.lastname: Tiberi
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Siena, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Tintori
authors.affiliation: University Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Elisa Rita
authors.initials: ER
authors.lastname: Ceresola
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Siena, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Fazi
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Siena, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Zamperini
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Siena, Italy.
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Calandro
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Siena, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Franchi
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Siena, Italy.
authors.forename: Manikandan
authors.initials: M
authors.lastname: Selvaraj
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Siena, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Botta
authors.affiliation: University Vita-Salute San Raffaele, Milan, Italy Ospedale San Raffale, Milan, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Sampaolo
authors.affiliation: University Vita-Salute San Raffaele, Milan, Italy Ospedale San Raffale, Milan, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Saita
authors.affiliation: Ospedale San Raffale, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ferrarese
authors.affiliation: University Vita-Salute San Raffaele, Milan, Italy Ospedale San Raffale, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Clementi
authors.affiliation: Ospedale San Raffale, Milan, Italy Department of Clinical and Experimental Medicine, Università degli Studi dell'Insubria, Varese, Italy canducci.filippo@hsr.it botta.maurizio@gmail.com.
authors.forename: Filippo
authors.initials: F
authors.lastname: Canducci
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Siena, Italy Biotechnology College of Science and Technology, Temple University, Biolife Science Building, Philadelphia, Pennsylvania, USA canducci.filippo@hsr.it botta.maurizio@gmail.com.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Botta
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D015704:CD4 Antigens / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D015699:HIV Envelope Protein gp120 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D023581:HIV Fusion Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D062105:Molecular Docking Simulation; D011485:Protein Binding
chemical_list: D019380:Anti-HIV Agents; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D023581:HIV Fusion Inhibitors