Synthesis and evaluation of the activity of 1H-1,2,3-triazole-thiophene ester derivatives against Chikungunya virus

• Published in: The microbe 2025-03, Vol.6, p.100220, Article 100220
• Main Authors: Esteves, Priscilla O., Cirne-Santos, Claudio C., Barros, Caroline S., Gomes, Max W.L., Alves, Guilherme, Rabelo, Vitor Won-Held, Portella, Danielle P., Gonzaga, Daniel T.G., Costa, Dora C.S., da Silva, Fernando C., Ferreira, Vitor F., Teixeira, Valéria L., Paixão, Izabel C.N. de P.
• Format: Article
• Language: English
• Subjects: Antiviral activity; Arbovirus; Cell culture; Chikungunya; Trialoze
• ISSN: 2950-1946; 2950-1946
• DOI: 10.1016/j.microb.2024.100220

The Chikungunya virus (CHIKV), transmitted by mosquitoes, recently caused severe outbreaks from the Indian Ocean to the Americas. Despite prior research on alphaviruses, little was understood about CHIKV's biology during the 2005 epidemic. This study tested 16 esters of 1H-1,2,3-triazole-thiophene to assess their cytotoxicity and antiviral activity. Six substances (11d, 11 f, 11 h, 12c, 12d, and 12 f) showed low cytotoxicity and high potential in inhibiting CHIKV in both Vero cells and MG-63 osteoblasts. Effective concentrations (EC50) varied between 0.95 for substance 12 f and 1.5 for substance 11 f, indicating strong inhibitory effects. Compounds 11 f and 12c had virucidal effects, inhibiting approximately 70 % and 55 % of the virus, respectively. Substance 12 f displayed potent inhibition even 12 hours post-infection. Combining 12 f with Ribavirin showed a strong synergistic effect, enhancing antiviral activity. These compounds present potential as selective and effective agents against CHIKV, especially given their post-infection administration capability, potentially paving the way for novel drugs to combat CHIKV outbreaks. [Display omitted]