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A series of novel 1,2,3-triazole–etodolac hybrids (6a–l) were designed and synthesized as potent anti-cancer molecules. The synthesis strongly relied on Huisgen's 1,3-dipolar cycloaddition between etodolac azide 3 and substituted terminal alkynes 5a–l. The use of CH2Cl2 as a co-solvent with H2O increased the reaction rate and provided the corresponding 1,2,3-triazole–etodolac hybrids (6a–l) in excellent yields compared to other organic co-solvent systems. All the compounds were screened for their in vitro anticancer activity against human A549 cell lines and compounds 6e, 6f, 6h, 6j, and 6l were found to be the best anti-cancer molecules as compared to the marketed drug doxorubicin.

Design and synthesis of 1,2,3-triazole–etodolac hybrids as potent anticancer molecules