Synthesis, biological evaluation and computational studies of novel iminothiazolidinone benzenesulfonamides as potent carbonic anhydrase II and IX inhibitors.
Bioorg Chem
; 77: 381-386, 2018 04.
Article
in En
| MEDLINE
| ID: mdl-29421714
ABSTRACT
A series of iminothiazolidinone-sulfonamide hybrids (2a-k) was synthesized by heterocyclization of sulfanilamide thioureas with methyl bromoacetate and characterized by spectroscopic techniques, mass and elemental analysis. The synthesized derivatives were screened against four relevant human (h) isoforms of carbonic anydrases (CAs, EC 4.2.1.1) I, II, IV and IX. These enzymes are involved in a variety of diseases, including glaucoma, retinitis pigmentosa, epilepsy, arthritis, and tumors. Derivatives 2a-2k exhibited the best inhibitory activity against the cytosolyc hCA II (KIs are reaching the sub-nanomolar range, 0.41-37.8â¯nM) and against the tumor-associated isoform hCA IX (KIs are spanning between 24.3 and 368.3â¯nM). The binding mode of the reported iminothiazolidinone benzenesulfonamides within hCA II and IX catalytic clefts was investigated by docking studies.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sulfonamides
/
Benzenesulfonates
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Carbonic Anhydrase Inhibitors
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Carbonic Anhydrase II
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Thiazolidines
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Molecular Docking Simulation
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Carbonic Anhydrase IX
Limits:
Humans
Language:
En
Journal:
Bioorg Chem
Year:
2018
Document type:
Article
Affiliation country:
Pakistan