Synthesis, Characterization, and Biological Evaluation of Some Novel Quinoxaline Derivatives as Antiviral Agents

Abstract

Ethyl (6,7-dimethyl-2-oxo-3,4-dihydroquinoxalin-3-yl)acetate and ethyl (6-methyl-2-oxo-3,4-dihydroquinoxalin-3-yl)acetate (1a,b), 3-methylquinoxalin-2(1H)-one (4) and 1,4-dihydroquinoxaline-2,3-dione (11) were the starting precursors for nine novel quinoxaline compounds, 3a, 6, 10, 13, 15, 16, 17, 18, and 20, via adopting different nucleophilic reactions. The synthesized compounds were tested for their antiviral activity against HCV, HBV, HSV-1, and HCMV. Concomitantly, their safety profile was investigated as well as their selectivity against the viral strains. The Virology Unit at the University of Alabama recorded that two compounds, i.e., 1a and 20, exhibited highly potent activity against HCMV with lower IC values (<0.05 μM) compared to ganciclovir (IC = 0.59 μM). Compounds 1a and 20 also exhibited low cytotoxicity together with a high selectivity index.

Quinoxaline Derivatives as Antiviral Agents: A Systematic Review

“…Several quinoxaline derivatives were evaluated for their anti-HCV potential. Even though novel quinoxaline derivatives synthetized using ethyl (6,7-dimethyl-2-oxo-3,4-dihydroquinoxalin-3-yl)acetate 4 and ethyl (6-methyl-2-oxo-3,4-dihydroquinoxalin-3-yl)acetate 5 , 3-methylquinoxalin-2(1 H )-one, and 1,4-dihydroquinoxaline-2,3-dione as precursors failed to demonstrate any activity against HCV [ 31 ], in pyrido[2,3- g ]quinoxalinone series, 5-chloro-3-(thiophen-2-yl)pyrido[2,3- g ]quinoxaline-2(1 H )-one 16 ( Figure 11 ) was able to inhibit HCV replication in a subgenomic replication assay with EC 50 = 7.5 ± 0.5 µM. However, it was also cytotoxic for GS4.1 cells (CC 50 = 21 ± 20 µM) [ 37 , 38 , 55 ].…”

“…The synthesis of four new aldehydo-sugar-N-(3-phenylquinoxalin-2-yl)hydrazones 2a-d and their acyclic C-nucleoside analogues, 1-(4-phenyl- [1,2,4]triazolo [4,3-a]quinoxalin-1-yl)alditols 3a-d ( Figure 4) indicated that these compounds exhibited very weak antiviral activity against HSV-1 in a plaque reduction infectivity assay in comparison to aphidicolin taken as reference [30]. Recently, nine novel quinoxaline derivatives were synthetized via different nucleophilic reactions using ethyl (6,7-dimethyl-2-oxo-3,4-dihydroquinoxalin-3-yl)acetate 4 and ethyl (6-methyl-2-oxo-3,4-dihydroquinoxalin-3-yl)acetate 5, 3-methylquinoxalin-2(1H)-one, and 1,4dihydroquinoxaline-2,3-dione as precursors [31] (Table 3). When their antiviral activity against HCMV was compared to the standard drug ganciclovir (EC50 = 0.059 µM), two derivatives demonstrated higher activity, each with EC50 < 0.05 µM.…”

“…Notably, the toxicity of 4 and 8 (CC50 = 108.47 and >150 µM, respectively) was comparable to the reference drug (CC50 >150 µM) and compound 6 showed the poorest safety profile with CC50 = 2.34 µM. Recently, nine novel quinoxaline derivatives were synthetized via different nucleophilic reactions using ethyl (6,7-dimethyl-2-oxo-3,4-dihydroquinoxalin-3-yl)acetate 4 and ethyl (6-methyl-2-oxo-3,4dihydroquinoxalin-3-yl)acetate 5, 3-methylquinoxalin-2(1H)-one, and 1,4-dihydroquinoxaline-2,3-dione as precursors [31] (Table 3). When their antiviral activity against HCMV was compared to the standard drug ganciclovir (EC 50 = 0.059 µM), two derivatives demonstrated higher activity, each with EC 50 < 0.05 µM.…”

An insight on medicinal attributes of 1,2,4-triazoles

“…Nine quinoxaline derivatives were prepared and evaluated for their antiviral activity against hepatitis C virus (HCV), hepatitis B virus (HBV), HSV-1, and human cytomegalovirus HCMV by El-Zahabi [ 175 ]. The in vitro screening data indicated that the pyridinyl triazole derivative 198 ( Fig.…”

Facile Synthesis of Regioisomeric N‐Alkyl Substituted 3‐Methylene‐3,4‐dihydroquinoxalin‐2(1H)‐ones

“…Enaminones bearing a 3,4‐dihydroquinoxalin‐2(1 H )‐one core (QOs) are a promising class of biologically active compounds. They were found to exhibit anticancer, anti‐inflammatory, antidiabetic, analgesic, antiviral, and antimicrobial activities (Figure ). In addition, these compounds are versatile and available building blocks enabling synthesis of various quinoxaline‐based heterocyclic systems…”