Design, synthesis, and in vitro and in silico studies of 1,3,4-thiadiazole-thiazolidinone hybrids as carbonic anhydrase inhibitors

• Published in: New journal of chemistry 2023-07, Vol.47 (29), p.13710-13720
• Main Authors: Hosseini Nasab, Narges, Raza, Hussain, Eom, Young Seok, Hassan, Mubashir, Kloczkowski, Andrzej, Chetty, Lloyd Christopher, Kruger, Hendrik Gert, Kim, Song Ja
• Format: Article
• Language: English
• Subjects: Acetazolamide; Anticancer properties; Binding; Carbonic anhydrase; Hydrogen bonds; Inhibitors; Molecular docking; Synthesis; Thiadiazoles
• ISSN: 1144-0546; 1369-9261
• DOI: 10.1039/D3NJ01547E

In this study, a series of 1,3,4-thiadiazole-thiazolidinone derivatives (7a–j) were synthesized as carbonic anhydrase inhibitors. The in vitro carbonic anhydrase inhibitory activity of these synthesized compounds was determined and the results revealed that compound 7i (IC 50 = 0.402 ± 0.017 μM) is more potent than the standard reference acetazolamide (IC 50 = 0.998 ± 0.046 μM). Moreover, kinetic analysis was also performed to see the mode of binding with the target enzyme, and it was shown that compound 7i bound with the target in a competitive manner. All compounds were screened for antioxidant activity against DPPH and anticancer activity against A549 (human lung cancer cells), and the MTT assay results indicated that compounds 7a and 7d had more inhibitory growth. Moreover, compound 7i exhibited a good conformational state with hydrogen bond interactions within the receptor binding pocket according to molecular docking studies. Therefore, the novel compound 7i might be employed as a promising pharmacophore for potent and selective carbonic anhydrase inhibitors.