Quinoxaline Derivatives as Antiviral Agents: A Systematic Review

Abstract

Background: In recent decades, several viruses have jumped from animals to humans, triggering sizable outbreaks. The current unprecedent outbreak SARS-COV-2 is prompting a search for new cost-effective therapies to combat this deadly pathogen. Suitably functionalized polysubstituted quinoxalines show very interesting biological properties (antiviral, anticancer, and antileishmanial), ensuring them a bright future in medicinal chemistry.

Objectives: Focusing on the promising development of new quinoxaline derivatives as antiviral drugs, this review forms part of our program on the anti-infectious activity of quinoxaline derivatives.

Methods: Study compiles and discusses recently published studies concerning the therapeutic potential of the antiviral activity of quinoxaline derivatives, covering the literature between 2010 and 2020.

Results: A final total of 20 studies included in this review.

Conclusions: This review points to a growing interest in the development of compounds bearing a quinoxaline moiety for antiviral treatment. This promising moiety with different molecular targets warrants further investigation, which may well yield even more encouraging results regarding this scaffold.

Keywords: SAR; antiviral; biological applications; chemistry; quinoxaline.

Figure 1

Chemical structure of S-2720.

Figure 2

Flow diagram of study selection adapted from PRISMA [27].

Figure 3

Chemical structure of 1-(4-chloro-8-methyl[1,2,4]triazolo[4,3a]quinoxaline-1-yl)-3-phenyl thiourea 1.

Figure 4

Chemical structure of new series of aldehydo-sugar-N-(3-phenylquinoxalin-2-yl)hydrazones and their acyclic C-nucleoside analogues, 1-(4-phenyl-[1,2,4]triazolo[4,3-a]quinoxalin-1-yl)alditols.

Figure 5

Structure–activity relationship of novel quinoxaline derivatives with anti HCMV activity.

Figure 6

General structure of 2-aryl-2-hydroxy ethylamine substituted 1H,7H-pyrido[1,2,3-de.]quinoxaline-6-carboxamides synthetized.

Figure 7

General structures of 3-aminoquinoxalin-2(1H)-one derivatives and derivatives with pyrimidine ring linked to quinoxaline through sulfur exhibiting anti EBV antigen activation.

Figure 8

Structure of the lead compound 11 for poxvirus inhibition.

Figure 9

Chemical structure of quinoxaline derivatives.

Figure 10

Structure–activity relationship of novel series of quinoxaline-2-mercapto-acetyl-urea analogues.

Figure 11

5-chloro-3-(thiophen-2-yl)pyrido[2,3-g]quinoxaline-2(1H)-one 16.

Figure 12

Chemical structure of grazoprevir.

Figure 13

General structure of synthetized indoloquinoxalines and benzoindoloquinoxalines.

Figure 14

Chemical structure of HBY and HBQ.

Figure 15

Structure and model of the binding site of new gelatinase inhibitors.