AI Article Synopsis
- Researchers developed 28 new 1,2,3-triazole derivatives that function as dual inhibitors of carbonic anhydrase and cathepsin B enzymes, targeting four human CA isoforms: I, II, IX, and XII.
- The carboxylic acid derivatives showed low micromolar inhibition against hCA II, IX, and XII, with the 4-Fluorophenyl carboxylic acid derivative 6c identified as the most effective inhibitor of hCA IX and XII.
- In addition to inhibition of CA, the synthesized compounds also demonstrated activity against cathepsin B, with certain derivatives, specifically 5i and 6c, displaying cytotoxic effects on A549
Article Abstract
Herein, we report the design and synthesis of a library of 28 new 1,2,3-triazole derivatives bearing carboxylic acid and ester moieties as dual inhibitors of carbonic anhydrase (CA) and cathepsin B enzymes. The synthesised compounds were assayed in vitro for their inhibition potential against four human CA (hCA) isoforms, I, II, IX and XII. The carboxylic acid derivatives displayed low micromolar inhibition against hCA II, IX and XII in contrast to the ester derivatives. Most of the target compounds showed poor inhibition against the hCA I isoform. 4-Fluorophenyl appended carboxylic acid derivative 6c was found to be the most potent inhibitor of hCA IX and hCA XII with a K value of 0.7 μM for both the isoforms. The newly synthesised compounds showed dual inhibition towards CA as well as cathepsin B. The ester derivatives exhibited higher % inhibition at 10 M concentration as compared with the corresponding carboxylic acid derivatives against cathepsin B. The results from in silico studies of the target compounds with the active site of cathepsin B were found in good correlation with the in vitro results. Moreover, two compounds, 5i and 6c, showed cytotoxic activity against A549 lung cancer cells, with IC values lower than 100 μM.
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| http://dx.doi.org/10.1002/ardp.202300372 | DOI Listing |
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