Details

Autor(en) / Beteiligte

• Thacker, Pavitra S.
• Newaskar, Vaishnavi
• Angeli, Andrea
• Sigalapalli, Dilep Kumar
• Goud, Nerella Sridhar
• Chirra, Hepsibha
• Shaik, Afzal B.
• Arifuddin, Mohammed
• Supuran, Claudiu T.

Titel

Synthesis and biological evaluation of coumarin‐thiazole hybrids as selective carbonic anhydrase IX and XII inhibitors

Ist Teil von

• Archiv der Pharmazie (Weinheim), 2022-12, Vol.355 (12), p.e2200232-n/a

Ort / Verlag

Frankfurt: Wiley Subscription Services, Inc

Erscheinungsjahr

2022

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• A series of coumarin‐linked thiazoles (6a–p) was synthesized and the synthesized compounds were evaluated against human carbonic anhydrases (hCAs) IX and XII, which have been implicated in cancer. All the compounds exhibited selective inhibition of both isoforms. The designed compounds inhibited hCA IX in a moderate nanomolar to submicromolar range. The hCA XII was inhibited in a low to moderate nanomolar range. Compound 6o exhibited the best inhibition of hCA XII with a Ki value of 91.1 nM. The hydrolyzed form of compound 6o also exhibited favorable interactions as well as good docking scores with both the isoforms. Hence, this compound can be taken as a template for the design of selective and potent hCA XII inhibitors. Coumarin‐thiazole hybrids (6a–p) were synthesized and evaluated for their inhibitory potencies against the transmembrane tumor‐associated human carbonic anhydrase (hCA) isoforms IX and XII. They inhibited hCA IX in the nanomolar to submicromolar range and hCA XII in the nanomolar range. Compounds 6p and 6o were found to be the most promising compounds, with Ki values of 413.8 (hCA IX) and 91.1 nM (hCA XII), respectively.