Phthalazine Sulfonamide Derivatives as Carbonic Anhydrase Inhibitors. Synthesis, Biological and in silico Evaluation.
ChemMedChem
; : e202400147, 2024 May 07.
Article
em En
| MEDLINE
| ID: mdl-38713763
ABSTRACT
Carbonic Anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide involved in several biological processes. They show a wide diversity in tissue distribution and their subcellular localization. Twenty-two novel phthalazine derivatives were designed, synthesized, and evaluated against four human isoforms hCAâ
I, hCAâ
II, hCAâ
IX, and hCAâ
XII. Compounds appeared to be very active mostly against hCAâ
IX (7) and hCAâ
I (6) isoforms being more potent than reference drug acetazolamide (AAZ). Some compounds appeared to be very selective with a selectivity index up to 13.8. Furthermore, docking was performed for some of these compounds on all isoforms to understand the possible interactions with the active site. Additionally, the most active compounds against hCAâ
IX were subjected to cell viability assay. The anticancer activity of the compounds (3 a-d, 5 d, 5 i, and 5 m) was investigated using two human breast cancer cell lines, i. e. MCF-7 and MDA-MB-231 cells, and the normal counterpart, namely MCF10-A cells.
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MEDLINE
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En
Ano de publicação:
2024
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Article