Abstract
Herpes simplex virus is an important human pathogen responsible for a range of diseases from mild uncomplicated mucocutaneous infections to life-threatening ones. Currently, the emergence of Herpes simplex virus resistant strains increased the need for more effective and less cytotoxic drugs for Herpes treatment. In this work, we synthesized a series of oxoquinoline derivatives and experimentally evaluated the antiviral activity against acyclovir resistant HSV-1 strain as well as their cytotoxity profile. The most active compound (3b), named here as Fluoroxaq-3b, showed a promising profile with a better cytotoxicity profile than acyclovir. The theoretical analysis of the structure–activity relationship of these compounds revealed some stereoelectronic properties such as lower LUMO energy and lipophilicity, besides a higher polar surface area and number of hydrogen bond acceptor groups as important parameters for the antiviral activity. Fluoroxaq-3b showed a good oral theoretical bioavailability, according to Lipinski rule of five, with a promising profile for further in vivo analysis.
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Acknowledgments
We thank Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal Docente (CAPES Edital Nanobiotecnologia 2008) and Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) for the financial support and fellowships. The technical assistance of Samara, Hania, and Juliana Novais is gratefully acknowledged.
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Abreu, P.A., da Silva, V.A.G.G., Santos, F.C. et al. Oxoquinoline Derivatives: Identification and Structure–Activity Relationship (SAR) Analysis of New Anti-HSV-1 Agents. Curr Microbiol 62, 1349–1354 (2011). https://doi.org/10.1007/s00284-010-9860-6
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DOI: https://doi.org/10.1007/s00284-010-9860-6