Synthesis, molecular docking analysis and carbonic anhydrase I-II inhibitory evaluation of new sulfonamide derivatives

• Published in: Bioorganic chemistry Vol. 91; pp. 103153 - 103162
• Main Authors: Sağlık, Begüm Nurpelin, Çevik, Ulviye Acar, Osmaniye, Derya, Levent, Serkan, Çavuşoğlu, Betul Kaya, Demir, Yeliz, Ilgın, Sinem, Özkay, Yusuf, Koparal, Ali Savaş, Beydemir, Şükrü, Kaplancıklı, Zafer Asım
• Format: Journal Article
• Language: English
• Published: SAN DIEGO Elsevier Inc 01.10.2019; Elsevier
• Subjects: ADME; Biochemistry & Molecular Biology; Carbonic anhydrase; Chemistry; Chemistry, Organic; Cytotoxicity; Life Sciences & Biomedicine; Molecular docking; Physical Sciences; Science & Technology; Sulfonamide; Cytotoxicity; Sulfonamide; Carbonic anhydrase; ADME; Molecular docking; ANALOGS; COMPLEXES; DRUG DESIGN; ISOZYMES I; SOLUBILITY; POTENT; HYDRAZONE; BIOLOGICAL EVALUATION; XII; ISOFORMS I
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2019.103153

Three-dimensional binding mode of compounds 3e and 3m in the enzyme active site of CA I (CA I PDB Code: 1AZM) and CA II (CA II PDB Code: 3HS4), respectively. [Display omitted] •New sulfonamide-hydrazone derivatives (3a-3n) were synthesized.•Synthesized compounds were evaluated for their inhibitory effects on purified human carbonic anhydrase (hCA) I and II.•The compound 3e demonstrated the best hCA I inhibitory effect with a Ki value of 0.1676 ± 0.017 µM.•The compound 3m showed the best hCA II inhibitory effect with a Ki value of 0.2880 ± 0.080 µM.•Molecular docking studies were performed to investigate the interaction types between active compounds and hCA enzymes. New sulfonamide-hydrazone derivatives (3a-3n) were synthesized to evaluate their inhibitory effects on purified human carbonic anhydrase (hCA) I and II. The inhibition profiles of the synthesized compounds on hCA I-II isoenzyme were investigated by comparing their IC50 and Ki values. Acetazolamide (5-acetamido-1,3,4-thiadiazole-2-sulfonamide, AZA) has also been used as a standard inhibitor. The compound 3e demonstrated the best hCA I inhibitory effect with a Ki value of 0.1676 ± 0.017 µM. Besides, the compound 3m showed the best hCA II inhibitory effect with a Ki value of 0.2880 ± 0.080 µM. Cytotoxicity of the compounds 3e and 3m toward NIH/3T3 mouse embryonic fibroblast cell line was observed and the compounds were found to be non-cytotoxic. Molecular docking studies were performed to investigate the interaction types between active compounds and hCA enzymes. Pharmacokinetic profiles of compounds were assessed by theoretical ADME predictions. As a result of this study a novel and potent class of CA inhibitors were identified with a good activity potential.