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

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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2747-2759
Number of pages13
JournalJournal of Medicinal Chemistry
Volume59
Issue number6
DOIs
Publication statusPublished - Mar 24 2016

Fingerprint

Reverse Transcriptase Inhibitors
Anti-Infective Agents
Anti-HIV Agents
Gels
HIV
Foams and Jellies Vaginal Creams
Viral DNA
Acquired Immunodeficiency Syndrome
Mutation
Genes
In Vitro Techniques

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

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. / Tintori, Cristina; Brai, Annalaura; Dasso Lang, Maria Chiara; Deodato, Davide; Greco, Antonia Michela; Bizzarri, Bruno Mattia; Cascone, Lorena; Casian, Alexandru; Zamperini, Claudio; Dreassi, Elena; Crespan, Emmanuele; Maga, Giovanni; Vanham, Guido; Ceresola, Elisa; Canducci, Filippo; Ariën, Kevin K.; Botta, Maurizio.

In: Journal of Medicinal Chemistry, Vol. 59, No. 6, 24.03.2016, p. 2747-2759.

Research output: Contribution to journalArticle

Tintori, C, Brai, A, Dasso Lang, MC, Deodato, D, Greco, AM, Bizzarri, BM, Cascone, L, Casian, A, Zamperini, C, Dreassi, E, Crespan, E, Maga, G, Vanham, G, Ceresola, E, Canducci, F, Ariën, KK & Botta, M 2016, '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', Journal of Medicinal Chemistry, vol. 59, no. 6, pp. 2747-2759. https://doi.org/10.1021/acs.jmedchem.5b01979
Tintori, Cristina ; Brai, Annalaura ; Dasso Lang, Maria Chiara ; Deodato, Davide ; Greco, Antonia Michela ; Bizzarri, Bruno Mattia ; Cascone, Lorena ; Casian, Alexandru ; Zamperini, Claudio ; Dreassi, Elena ; Crespan, Emmanuele ; Maga, Giovanni ; Vanham, Guido ; Ceresola, Elisa ; Canducci, Filippo ; Ariën, Kevin K. ; Botta, Maurizio. / 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. In: Journal of Medicinal Chemistry. 2016 ; Vol. 59, No. 6. pp. 2747-2759.
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