3-Hydrazinoisatin-based benzenesulfonamides as novel carbonic anhydrase inhibitors endowed with anticancer activity: Synthesis, in vitro biological evaluation and in silico insights

0512137 - ÚEB 2020 RIV FR eng J - Journal Article
Abo-Ashour, M. F. - Eldehna, W. M. - Nocentini, A. - Bonardi, A. - Bua, S. - Ibrahim, H. S. - Elaasser, M. M. - Kryštof, Vladimír - Jorda, Radek - Gratteri, P. - Abou-Seri, S. M. - Supuran, C.T.
3-Hydrazinoisatin-based benzenesulfonamides as novel carbonic anhydrase inhibitors endowed with anticancer activity: Synthesis, in vitro biological evaluation and in silico insights.
European Journal of Medicinal Chemistry. Roč. 184, Dec 15 (2019), č. článku 111768. ISSN 0223-5234. E-ISSN 1768-3254
Institutional support: RVO:61389030
Keywords : Anticancer * Benzenesulfonamides * Carbonic anhydrase inhibitors * Colony forming assay * Molecular dynamics
OECD category: Oncology
Impact factor: 5.573, year: 2019
Method of publishing: Open access
http://dx.doi.org/10.1016/j.ejmech.2019.111768

Herein we describe the design and synthesis of two series of sulfonamides featuring N-unsubstituted (4a-c) or N-substituted (7a-o) isatin moieties (as tails) connected to benzenesulfonamide moiety via a hydrazine linker. All the prepared sulfonamides (4a-c and 7a-o) showed potent inhibitory activities toward transmembrane tumor-associated human (h) carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, IX and XII with KI range (8.3–65.4 nM) and (11.9–72.9 nM), respectively. Furthermore, six sulfonamides (7e, 7i, 7j, 7m, 7n and 7o) were assessed for their anti-proliferative activity, according to US-NCI protocol, toward a panel of sixty cancer cell lines. Compounds 7j and 7n were the most promising counterparts in this assay displaying broad spectrum anti-proliferative activity toward diverse cell lines. Also, sulfonamide 7n significantly inhibited clonogenicity of HCT-116 cells in a concentration dependent manner in the colony forming assay. Moreover, molecular modeling studies were performed to gain insights for the plausible binding interactions and affinities for the target isatin-based sulfonamides (4a-c and 7a-o) within hCA isoforms II and IX active sites.
Permanent Link: http://hdl.handle.net/11104/0302347