1. 3-Hydrazinoisatin-based benzenesulfonamides as novel carbonic anhydrase inhibitors endowed with anticancer activity: Synthesis, in vitro biological evaluation and in silico insights.
- Author
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Abo-Ashour MF, Eldehna WM, Nocentini A, Bonardi A, Bua S, Ibrahim HS, Elaasser MM, Kryštof V, Jorda R, Gratteri P, Abou-Seri SM, and Supuran CT
- Subjects
- Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Carbonic Anhydrase Inhibitors chemical synthesis, Carbonic Anhydrase Inhibitors chemistry, Cell Proliferation drug effects, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Humans, Hydrazines chemistry, Isatin chemistry, Molecular Docking Simulation, Molecular Structure, Structure-Activity Relationship, Sulfonamides chemical synthesis, Sulfonamides chemistry, Tumor Cells, Cultured, Benzenesulfonamides, Antineoplastic Agents pharmacology, Carbonic Anhydrase Inhibitors pharmacology, Carbonic Anhydrases metabolism, Hydrazines pharmacology, Isatin pharmacology, Sulfonamides pharmacology
- Abstract
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 K
I 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., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)- Published
- 2019
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