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

详细信息    查看全文

• 作者：Cristina Tintori ; Annalaura Brai ; Maria Chiara Dasso Lang ; Davide Deodato ; Antonia Michela Greco ; Bruno Mattia Bizzarri ; Lorena Cascone ; Alexandru Casian ; Claudio Zamperini ; Elena Dreassi ; Emmanuele Crespan ; Giovanni Maga ; Guido Vanham ; Elisa Ceresola ; Filippo Canducci ; Kevin K. Ariën ; Maurizio Botta
• 刊名：Journal of Medicinal Chemistry
• 出版年：2016
• 出版时间：March 24, 2016
• 年：2016
• 卷：59
• 期：6
• 页码：2747-2759
• 全文大小：560K
• ISSN：1520-4804

文摘

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.