Design, synthesis and molecular docking studies of novel benzimidazole-1,3,4-oxadiazole hybrids for their carbonic anhydrase inhibitory and antioxidant effects.

In this study, eleven new compounds with a series of benzimidazole-1,3,4-oxadiazole derivatives structures were synthesized and evaluated for their human (h) carbonic anhydrase inhibitory activities against two isoforms hCA I, hCA II, and antioxidant activity. The synthesized compounds were fully characterized by spectral analysis methods such as ¹H-NMR, ¹³C-NMR, and HRMS. Compared to acetazolamide (IC₅₀ = 2.26 µM) for hCA I, the most potent compound 4a was with the IC₅₀ value of 1.322 µM and compound 4d is the other molecule with a greater IC₅₀ value (IC₅₀ = 1.989 µM) than that of acetazolamide in these series. Among all the compounds, 4a (1.826 µM), 4d (1.502 µM), and 4g (1.886 µM) are the most active hybrids against carbonic hCA II. Considering that compound 4a containing 4-bromophenyl structure is effective on both hCA I and hCA II, it can be considered as a promising structure for the development of effective candidates with potent CA inhibitory activities. TAS assay was used to evaluate the antioxidant activities of synthesized compounds. The synthesized compound was analyzed for their in vitro cytotoxic activity on the L929 cell line by using MTT assay. In the last step of this study, molecular docking studies were performed in order to compare the biological activities of the most active molecules against the enzymes of hCAI and hCA II. [ABSTRACT FROM AUTHOR]