title: Design and synthesis of novel 4-(4-oxo-2-arylthiazolidin-3-yl)benzenesulfonamides as selective inhibitors of carbonic anhydrase IX over I and II with potential anticancer activity.
abstract: The novel 4-(4-oxo-2-arylthiazolidin-3-yl)benzenesulfonamide derivatives were designed and synthesized for selective carbonic anhydrase IX (CA IX) inhibitory activity with anticancer potential. In the CA inhibition assay, 3f was found to be the most potent and selective inhibitor of CA IX with inhibitory constant (K(I)) value of 2.2 nM. Among the synthesized compounds, 3f showed IC₅₀ values of 5.03 μg/ml (cisplatin: 6.56 μg/ml), 5.81 μg/ml (cisplatin: 5.85 μg/ml), and 23.93 μg/ml (cisplatin: 2.75 μg/ml) against COLO-205, MDA-MB-231, and DU-145 cell lines, respectively. At IC₅₀, 3f caused cell shrinkage, nuclear condensation, and nuclear fragmentation events characteristic to apoptosis in the Hoechst 33258 and acridine orange-ethidium bromide staining studies of COLO-205 cells. In the Dalton's lymphoma ascites (DLA) solid tumor model 3f decreased tumor volume by 64.83% (cisplatin: 71.62%), while increase in mean body weight was found to be only 4.09% (cisplatin: 3.47%).
authors.affiliation: Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal 576104, Karnataka, India. Electronic address: sharadpune_2009@yahoo.com.
authors.forename: Sharad Kumar
authors.initials: SK
authors.lastname: Suthar
authors.forename: Sumit
authors.initials: S
authors.lastname: Bansal
authors.forename: Sandeep
authors.initials: S
authors.lastname: Lohan
authors.forename: Vikarm
authors.initials: V
authors.lastname: Modak
authors.forename: Anil
authors.initials: A
authors.lastname: Chaudhary
authors.forename: Amit
authors.initials: A
authors.lastname: Tiwari
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D024401:Carbonic Anhydrase I / Q000737:chemistry / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000737:chemistry / Q000378:metabolism; D000071231:Carbonic Anhydrase IX; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002256:Carbonic Anhydrases / Q000737:chemistry / Q000378:metabolism*; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D000096926:Benzenesulfonamides
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II; D000071231:Carbonic Anhydrase IX; D002257:Carbonic Anhydrase Inhibitors; D002256:Carbonic Anhydrases; D013449:Sulfonamides; D000096926:Benzenesulfonamides; C089226:CA9 protein, human
keywords: (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; AO; Anticancer; Benzenesulfonamide; CA; Carbonic anhydrase IX; Cell lines; DCC; DLA; Daltion's lymphoma ascites; Dalton's lymphoma ascites; EB; HIF-1; MTT; N,N-dicyclohexylcarbodiimide; OECD; Organisation for Economic Cooperation and Development; Thiazolidin-4-one; acridine orange; carbonic anhydrase; ethidium bromide; hypoxia-inducible transcription factor-1