Development of benzene and benzothiazole-sulfonamide analogues as selective inhibitors of the tumor-associated carbonic anhydrase IX

Manzoor, S and Angeli, A and Zara, S and Carradori, S and Rahman, MA and Raza, MK and Supuran, CT and Hoda, N (2022) Development of benzene and benzothiazole-sulfonamide analogues as selective inhibitors of the tumor-associated carbonic anhydrase IX. In: European Journal of Medicinal Chemistry, 243 .

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Abstract

With an aim to develop novel potential antitumor agents, two series of benzene- and benzothiazole-sulfonamide derivatives, acting as effective human carbonic anhydrase (hCA, EC 4.2.1.1) inhibitors, have been developed using the tail approach. The synthesized compounds (XS-1 to XS-22) were assayed for the inhibition of physiologically relevant isoforms of hCA, the cytosolic CA I and II, the membrane-bound CA IV and tumor-associated CA IX. It was found the compounds of both series displayed low to medium nanomolar range inhibition against CA I, II and IX, and weak inhibition against CA IV. Some of the derivatives displayed selective inhibition towards tumor-associated CA IX isoform, within the nanomolar range. These potent compounds were also screened for their selective toxicity to evaluate their in vitro anti-proliferative effects on Human Gingival Fibroblasts (HGFs) and breast adenocarcinoma cell line (MCF7). Lastly, molecular docking studies were carried out to explain those structural requirements that were liable for the discrimination among selected human carbonic anhydrase isoforms.

Item Type:	Journal Article
Publication:	European Journal of Medicinal Chemistry
Publisher:	Elsevier Masson s.r.l.
Additional Information:	The copyright for this article belongs to Elsevier Masson s.r.l.
Keywords:	Anti-proliferative; Benzene and benzothiazole-sulfonamide; Carbonic anhydrase inhibitors; Molecular docking; Selective hCA IX inhibition
Department/Centre:	Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited:	28 Oct 2022 05:16
Last Modified:	28 Oct 2022 05:16
URI:	https://eprints.iisc.ac.in/id/eprint/77614

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