Synthesis, molecular modelling and QSAR study of new N-phenylacetamide-2-oxoindole benzensulfonamide conjugates as carbonic anhydrase inhibitors with antiproliferative activity

In continuation of our previous studies to optimise potent carbonic anhydrase inhibitors, two new series of isatin N-phenylacetamide based sulphonamides were synthesised and screened for their human (h) carbonic anhydrase (EC 4.2.1.1) inhibitory activities against four isoforms hCA I, hCA II, hCA IX...

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Published in:Journal of enzyme inhibition and medicinal chemistry 2022-12, Vol.37 (1), p.701-717
Main Authors: Said, Mona F., George, Riham F., Petreni, Andrea, Supuran, Claudiu T., Mohamed, Nada M.
Format: Article
Language:English
Subjects:
2D-QSAR study
Acetanilide
Acetazolamide
benzenesulfonamides
Cancer
Carbon dioxide
Carbonic anhydrase inhibitors
Carbonic anhydrases
Chemistry
Cytotoxicity
Enzymes
Functional foods & nutraceuticals
Isoforms
molecular docking
Molecular modelling
Pharmaceutical sciences
Pharmacy
Research Paper
Structure-activity relationships
Sulfonamides
Tumors
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Summary:In continuation of our previous studies to optimise potent carbonic anhydrase inhibitors, two new series of isatin N-phenylacetamide based sulphonamides were synthesised and screened for their human (h) carbonic anhydrase (EC 4.2.1.1) inhibitory activities against four isoforms hCA I, hCA II, hCA IX and hCA XII. The indole-2,3-dione derivative 2h showed the most effective inhibition profile against hCAI and hCA II (K I = 45.10, 5.87 nM) compared to acetazolamide (AAZ) as standard inhibitor. Moreover, 2h showed appreciable inhibition activity against the tumour-associated hCA XII, similar to AAZ showing K I of 7.91 and 5.70 nM, respectively. The analogs 3c and 3d showed good cytotoxicity effects, and 3c revealed promising selectivity towards lung cell line A549. Molecular docking was carried out for 2h and 3c to predict their binding conformations and affinities towards the hCA I, II, IX and XII isoforms.
ISSN:1475-6366
1475-6374
DOI:10.1080/14756366.2022.2036137