Potential of several triazene derivatives against DENGUE viruses

• Published in: Bioorganic & medicinal chemistry letters 2024-03, Vol.101, p.129646-129646, Article 129646
• Main Authors: Sokhna, Seynabou, Mérindol, Natacha, Presset, Marc, Seck, Insa, Girard, Marie-Pierre, Ka, Seydou, Ndoye, Samba Fama, Ba, Aïcha Lalla, Samb, Issa, Berthoux, Lionel, Le Gall, Erwan, Desgagné-Penix, Isabel, Seck, Matar
• Format: Article
• Language: English
• Subjects: Anti-dengue; Cytotoxicity; DENV; Fever; Triazene
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2024.129646

[Display omitted] •Significant inhibitory effect of triazenes against DENV infection of Huh7 cells (1.56-8.45 μM) with low cytotoxicity (100 μM).•Phenyl group at N1 and the pyridine at N3 of the triazene promotes antiviral activity.•Electron-withdrawing groups such as CF3, improves the antiviral activity.•Anti-DENV activities and the cytotoxicity of triazenes observed suggest a possible role in targeting infectious disease. Dengue fever is an infectious disease caused by the dengue virus (DENV), an RNA Flavivirus transmitted by the mosquitoes Aedes aegypti and Aedes albopictus widespread in tropical, subtropical and also temperate regions. Symptoms range from a simple cold to a severe, life-threatening haemorrhagic fever. According to the WHO, it affects around 390 million people per year. No antiviral treatment for DENV is available, and the Dengvaxia vaccine is only intended for people over 9 years of age who have contracted dengue one time in the past, and shows serotype-specific effectiveness. There is therefore a crying need to discover new molecules with antiviral power against flaviviruses. The present study was carried out to evaluate the anti-DENV activities and cytotoxicity of triazenes obtained by diazocopulation. Some triazenes were highly cytotoxic (16, and 25) to hepatocarcinoma Huh7 cells, whereas others displayed strong anti-DENV potential. The antiviral activity ranged from EC50 = 7.82 µM to 48.12 µM in cellulo, with a selectivity index (CC50/EC50) greater than 9 for two of the compounds (10, and 20). In conclusion, these new triazenes could serve as a lead to develop and optimize drugs against DENV.