1. Sulfonamide-Based Azaheterocyclic Schiff Base Derivatives as Potential Carbonic Anhydrase Inhibitors: Synthesis, Cytotoxicity, and Enzyme Inhibitory Kinetics.
- Author
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Abas M, Rafique H, Shamas S, Roshan S, Ashraf Z, Iqbal Z, Raza H, Hassan M, Afzal K, Rizvanov AA, and Asad MHHB
- Subjects
- Acetazolamide, Carbonic Anhydrases drug effects, Carbonic Anhydrases metabolism, Cell Line, Tumor, Cell Survival drug effects, Humans, Kinetics, MCF-7 Cells, Molecular Docking Simulation, Carbonic Anhydrase Inhibitors chemical synthesis, Carbonic Anhydrase Inhibitors chemistry, Carbonic Anhydrase Inhibitors pharmacology, Schiff Bases, Sulfonamides
- Abstract
A series of sulfonamide-bearing azaheterocyclic Schiff base derivatives 3(a-j) were synthesized as carbonic anhydrase inhibitors. The substituted benzene sulfonyl chlorides 1(a-d) were reacted with N
2 H4 to get aromatic sulfonyl hydrazides 2(a-d) . The intermediate hydrazides 2(a-d) were treated with substituted aldehydes to afford azaheterocyclic sulfonamide Schiff bases 3(a-j) . The spectral data of synthesized compounds confirmed the formation of the final products. The inhibitory effects of 3(a-j) on carbonic anhydrase activity were determined, and it was found that derivative 3c exhibited the most potent activity with IC50 0.84 ± 0.12 μ M among all other derivatives and is also more active than standard acetazolamide (IC50 0.91 ± 0.12). The enzyme inhibitory kinetics results determined by Lineweaver-Burk plots revealed that compound 3c inhibits the enzyme by noncompetitive mode of inhibition with Ki value 8.6 μ M. The molecular docking investigations of the synthesized analogues 3(a-j) may serve as core structure to project carbonic anhydrase inhibitors with greater potency.3c may serve as core structure to project carbonic anhydrase inhibitors with greater potency., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2020 Mujahid Abas et al.)- Published
- 2020
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