Synthesis, crystal structure, and reactive oxygen species (ROS) inhibition of N– and O–linked triazole analogues of harmine

•Syntheses of two new series of N– and O–linked triazole analogues of harmine are reported.•Crystal structures of a triazole and few precursor molecules are reported.•Most of the compounds showed potent ROS inhibitory activity with IC50 values between 1.1 - 7.5 µg/mL.•Series could emerge as a therapeutic potential in developing new anti-inflammatory agents. Reactive oxygen species (ROS) have been reported in the literature for their important role in the progression of oxidative stress which results in several pathological conditions, including Alzheimer's and Parkinson's disease, cancer, arthritis, diabetes, atherosclerosis, and autoimmune disease. Anti-inflammatory agents are important to control over production of ROS. However, several side effects are associated with the reported marketed drugs. In present study, two new series of harmine linked–triazoles (5–25) were designed as potential anti-inflammatory agents, based on the reported anti-inflammatory effect of harmine alkaloid. Triazole compounds were prepared via copper-catalyzed 1,3-dipolar cycloaddition reaction between azidoacetophenones and N-propargyl harmine under green conditions with high yields and short reaction times. Compounds 2, 3, 6–8, 10, 12, 14, 17, 19, 20, and 22 showed a potent ROS inhibitory activity with IC50 values between 1.1 ± 0.1 to 7.5 ± 0.7 µg/mL, compared to the standard, ibuprofen (IC50 = 11.2 ± 1.9 µg/mL). Also, compounds are found to be non-cytotoxic against NIH 3T3 cell line, except a small set of compounds, including 9, 12, 21, and 25. The synthesized harmine-linked triazoles may emerge as attractive building blocks in the search of new anti-inflammatory agents. [Display omitted]