Antiviral Activity of Novel Quinoline Derivatives against Dengue Virus Serotype 2

Abstract

Dengue virus causes dengue fever, a debilitating disease with an increasing incidence in many tropical and subtropical territories. So far, there are no effective antivirals licensed to treat this virus. Here we describe the synthesis and antiviral activity evaluation of two compounds based on the quinoline scaffold, which has shown potential for the development of molecules with various biological activities. Two of the tested compounds showed dose-dependent inhibition of dengue virus serotype 2 in the low and sub micromolar range. The compounds 1 and 2 were also able to impair the accumulation of the viral envelope glycoprotein in infected cells, while showing no sign of direct virucidal activity and acting possibly through a mechanism involving the early stages of the infection. The results are congruent with previously reported data showing the potential of quinoline derivatives as a promising scaffold for the development of new antivirals against this important virus.

Recent Advances in the Synthesis and Biological Activity of 8-Hydroxyquinolines

“…A few publications have dealt with the antiviral activities of 8-HQ and its derivatives. De la Guardia et al described the synthesis of novel 8-hydroxyquinoline derivatives ( Scheme 1 ) and investigated their activity against dengue virus [ 7 ]. These researchers prepared a number of compounds from 8-hydroxyquinoline N-oxide 2 , which upon treatment with copper-catalyzed Grignard reagents (RMgX; R = i -Pr and i -Bu) gave 2-alkyl-8-hydroxyquinoline 3 .…”

Antimalarial drugs and their metabolites are potent Zika virus inhibitors

“…DAQ and DECQ exhibited in vitro anti‐ZIKV activity similar to other quinoline derivatives such as AQ, CQ, HCQ, quinacrine, mefloquine, and GSK369796 . According to these results, it might be logical that quinoline should be a promising scaffold in the design of novel CQ and AQ analogs that could bear improved inhibitory activities. To further improve their potency, structure‐activity study is needed to guide the synthesis of novel quinoline derivatives that may have improved potency and/or toxicity.…”

Synthesis and Biological Evaluation of New 1,2,3‐Triazolyl‐Pyrazolyl‐Quinoline Derivatives as Potential Antimicrobial Agents

“…They showed antibacterial and antifungal, antitubercular, anticancer, antioxidant, anti‐inflammatory and antipyretic activities. Quinoline tethered azole hybrids are important pharmacophores that possess a wide range of biological activities . The 1,2,3‐triazole nucleus containing compounds are important pharmacophore for drug development as they also exhibit significant biological activities …”