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

Molecules

MªÁngeles Castro¹  PabloA. García¹  Arturo San Feliciano¹  VickyC. Roa-Linares²  Verónica Tangarife-Castaño²  Liliana Betancur-Galvis²  Yaneth Miranda-Brand²  Rodrigo Ochoa³ 

[1] Departamento de Ciencias Farmacéuticas, Área de Química Farmacéutica, Facultad de Farmacia, CIETUS, IBSAL. Campus Miguel de Unamuno, University of Salamanca, 37007-Salamanca, Spain;Group of Investigative Dermatology, Institute of Medical Research, Faculty of Medicine, University of Antioquia, Medellin 050010, Colombia;Programa de Estudio y Control de Enfermedades Tropicales PECET, Facultad de Medicina, University of Antioquia, Medellín 050010, Colombia;

关键词: terpenylquinones;    naphthoquinones;    anthraquinones;    antiviral activity;    herpesvirus;    dengue virus;    cytotoxicity;   

DOI  :  10.3390/molecules24071279

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown