Sulfonamide-Based Azaheterocyclic Schiff Base Derivatives as Potential Carbonic Anhydrase Inhibitors: Synthesis, Cytotoxicity, and Enzyme Inhibitory Kinetics.

A series of sulfonamide-bearing azaheterocyclic Schiff base derivatives were synthesized as carbonic anhydrase inhibitors. The substituted benzene sulfonyl chlorides were reacted with NH to get aromatic sulfonyl hydrazides . The intermediate hydrazides were treated with substituted aldehydes to afford azaheterocyclic sulfonamide Schiff bases . The spectral data of synthesized compounds confirmed the formation of the final products. The inhibitory effects of on carbonic anhydrase activity were determined, and it was found that derivative exhibited the most potent activity with IC0.84 ± 0.12 M among all other derivatives and is also more active than standard acetazolamide (IC0.91 ± 0.12). The enzyme inhibitory kinetics results determined by Lineweaver-Burk plots revealed that compound inhibits the enzyme by noncompetitive mode of inhibition with value 8.6 M. The molecular docking investigations of the synthesized analogues were evaluated which assured that synthesized compounds bind well inside the active binding site of the target enzyme. Cytotoxicity on human keratinocyte (HaCaT) and MCF-7 cell lines was performed, and it was found that most of the synthesized analogues were nontoxic on these cell lines and the toxic effects follow the dose-dependent manner. Based on our investigations, it was suggested that analogue may serve as core structure to project carbonic anhydrase inhibitors with greater potency.