Synthesis and biological evaluation of some coumarin hybrids as selective carbonic anhydrase IX and XII inhibitors.

Autor: Thacker PS; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad 500037, India., Sridhar Goud N; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad 500037, India., Argulwar OS; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad 500037, India., Soman J; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad 500037, India., Angeli A; Università degli Studi di Firenze, Neurofarba Dept., Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy., Alvala M; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad 500037, India., Arifuddin M; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad 500037, India; Department of Chemistry, Anwarul Uloom College, 11-3-918, New Malleypally, Hyderabad 500001, T. S., India. Electronic address: arif@niperhyd.ac.in., Supuran CT; Università degli Studi di Firenze, Neurofarba Dept., Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy. Electronic address: claudiu.supuran@unifi.it.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2020 Nov; Vol. 104, pp. 104272. Date of Electronic Publication: 2020 Sep 08.
DOI: 10.1016/j.bioorg.2020.104272
Abstrakt: Two series, coumarin-linked to thiazolidinone via a pyrazole linker (6a-m, Series 1) and coumarin-linked 1,2,3-triazoles (5a-j, Series 2) were synthesized and the synthesized compounds were subjected for evaluation against the four physiologically and pharmacologically relevant hCA isoforms, hCA I, II, IX and XII. The results indicated selective inhibition of tumor-associated isoforms hCA IX and XII over the off-target isoforms, hCA I and II. The compounds of series 1 exhibited better hCA IX inhibition compared to hCA XII, with compounds 6i, 6h, 6a and 6k, exhibiting notable K i values of less than 100 nM. Among all the compounds, compound 6i showed the best inhibition with a K i value of 61.5 nM. Among the compounds of series 2, compounds 5a, 5b, 5c, 5d, 5f and 5j exhibited notable hCA IX inhibition. Compound 5d showed the best inhibition with a K i value of 32.7 nM. In the case of hCA XII, compound 5i showed the best inhibition with a K i value of 84.2 nM. Hence, compound 6i from Series 1 and 5d from Series 2 could be taken as lead compounds for the further development of selective and potent hCA IX inhibitors, whereas the compound 5i from Series 2 can be explored further for the design of selective and potent hCA XII inhibitors.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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