Nonsteroidal anti‐inflammatory drugs based new 1,2,3‐triazole derivatives: Their design, one‐pot synthesis and in vitro evaluation

• Published in: Journal of heterocyclic chemistry 2021-10, Vol.58 (10), p.2018-2032
• Main Authors: Kuntala, Naveen, Mareddy, Jyoti, Telu, Jhonsee Rani, Banothu, Venkanna, Pal, Sarbani, Anireddy, Jaya Shree
• Format: Article
• Language: English
• Subjects: Alkynes; Chemical reactions; Cycloaddition; Ibuprofen; Naproxen; Nonsteroidal anti-inflammatory drugs; Quinoline; Toxicity; Triazoles
• ISSN: 0022-152X; 1943-5193
• DOI: 10.1002/jhet.4328

A series of novel and small molecules containing structural features of some well‐known nonsteroidal anti‐inflammatory drugs (NSAIDs) such as mefenamic acid or ibuprofen or naproxen and a heterocyclic moiety, for example, benzoxepine or quinoline were designed where a substituted 1,2,3‐triazole was used as a linker. These molecules were initially designed as potential antibacterial agents. Synthesis of these compounds was carried out using a Cu‐catalyzed azide‐alkyne cycloaddition (CuAAC) as the key step to construct the central 1,2,3‐triazole ring. The methodology involved regioselective and in situ azide formation from a dichloro derivative of heterocycle followed by click reaction with the appropriate alkyne containing the NSAID framework in the same pot. This one‐pot sequential reaction afforded 24 target compounds in good yields. To assess their antibacterial properties, all the synthesized compounds were tested against both Gram‐positive and Gram‐negative species bacterial strains. One compound was found to be effective against the Gram‐negative species P. aeruginosa. This compound also showed selective cytotoxicity against two cancer cell lines (COLO‐205 and HOP‐62) but no significant effect against noncancerous cell line (HEK293).