A number of pre-designed benzoxepine-1,2,3-triazole hybrids were synthesized for the first time using a Cu catalyzed azide-alkyne cycloaddition (CuAAC) strategy. Thus a 10
These compounds were generally found to be effective towards gram -ve species and one of them showed selective cytotoxicity against lung cancer cell line.
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 Cucatalyzed 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 Gramnegative 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).
We describe the synthesis, characterization, and in vitro antibacterial evaluation of a library of novel compounds based on 1,2,3‐triazolo phosphonate framework along with the evaluation of DNA gyrase inhibitory potential of a promising molecule in silico. Preparation of these compounds was carried out via a multistep sequence comprising of the Abramov reaction followed by the Cu(I)‐catalyzed azide–alkyne cycloaddition (CuAAC) as the key steps. Various α‐hydroxyphosphonate derivatives containing either a secondary or tertiary alcohol at the α position were prepared. When screened for their antibacterial activities in vitro using a Gram‐positive (Staphylococcus aureus) and three Gram‐negative (Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa) strains, majority of these derivatives exhibited reasonable to good effects with the analogue 5k being active against all the strains. The SAR analysis indicated that the activity was influenced by the position of the α‐hydroxyphosphonate moiety as well as the substituent present on the benzene ring attached to the 1,2,3‐triazole ring. Moreover, the compound 5k showed strong interactions with the DNA active site when docked into the DNA gyrase in silico. Thus, the 1,2,3‐triazolo phosphonate derivative 5k appeared to be a novel and promising hit molecule that deserves further study as a potential antibacterial agent.
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