Anti-Herpetic, Anti-Dengue and Antineoplastic Activities of Simple and Heterocycle-Fused Derivatives of Terpenyl-1,4-Naphthoquinone and 1,4-Anthraquinone

ABSTRACT: Quinones are secondary metabolites of higher plants associated with many biological activities, including antiviral effects and cytotoxicity. In this study, the anti-herpetic and anti-dengue evaluation of 27 terpenyl-1,4-naphthoquinone (NQ), 1,4-anthraquinone (AQ) and heterocycle-fused quinone (HetQ) derivatives was done in vitro against Human Herpesvirus (HHV) type 1 and 2, and Dengue virus serotype 2 (DENV-2). The cytotoxicity on HeLa and Jurkat tumor cell lines was also tested. Using plaque forming unit assays, cell viability assays and molecular docking, we found that NQ 4 was the best antiviral compound, while AQ 11 was the most active and selective molecule on the tested tumor cells. NQ 4 showed a fair antiviral activity against Herpesviruses (EC50: <0.4 µg/mL, <1.28 µM) and DENV-2 (1.6 µg/mL, 5.1 µM) on pre-infective stages. Additionally, NQ 4 disrupted the viral attachment of HHV-1 to Vero cells (EC50: 0.12 µg/mL, 0.38 µM) with a very high selectivity index (SI = 1728). The in silico analysis predicted that this quinone could bind to the prefusion form of the E glycoprotein of DENV-2. These findings demonstrate that NQ 4 is a potent and highly selective antiviral compound, while suggesting its ability to prevent Herpes and Dengue infections. Additionally, AQ 11 can be considered of interest as a leader for the design of new anticancer agents.

• Autores: Roa Linares, Vicky Constanza; Tangarife Castaño, Verónica; Betancur Galvis, Liliana Amparo; Miranda Brand, Yaneth de Jesús; Ochoa Deossa, Rodrigo Alonso; Ángeles Castro, María; San Feliciano Martin, Arturo; García, Pablo
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2019
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/40305
• Acceso en línea: https://hdl.handle.net/10495/40305
• Palabra clave: Anthraquinones; Antraquinonas; Antiviral Agents; Antivirales; Chlorocebus aethiops; Dengue Virus; Virus del Dengue; Naphthoquinones; Naphthoquinones; HeLa Cells; Células HeLa; Herpesviridae; Herpesvirus 1, Human; Herpesvirus Humano 1; Herpesvirus 2, Human; Herpesvirus Humano 2; Vero Cells; Células Vero; https://id.nlm.nih.gov/mesh/D000880; https://id.nlm.nih.gov/mesh/D000998; https://id.nlm.nih.gov/mesh/D002522; https://id.nlm.nih.gov/mesh/D003716; https://id.nlm.nih.gov/mesh/D009285; https://id.nlm.nih.gov/mesh/D006367; https://id.nlm.nih.gov/mesh/D006564; https://id.nlm.nih.gov/mesh/D018259; https://id.nlm.nih.gov/mesh/D018258; https://id.nlm.nih.gov/mesh/D014709
• Rights: openAccess
• License: https://creativecommons.org/licenses/by/4.0/