Synthesis of benzensulfonamides linked to quinazoline scaffolds as novel carbonic anhydrase inhibitors.

Autor: El-Azab AS; Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Electronic address: adelazab@ksu.edu.sa., Abdel-Aziz AA; Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Bua S; Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy., Nocentini A; Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy., El-Gendy MA; Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Mohamed MA; Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, AlKharj, Saudi Arabia; Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt., Shawer TZ; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt., AlSaif NA; Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Supuran CT; Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy. Electronic address: claudiu.supuran@unifi.it.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2019 Jun; Vol. 87, pp. 78-90. Date of Electronic Publication: 2019 Mar 06.
DOI: 10.1016/j.bioorg.2019.03.007
Abstrakt: Carbonic anhydrase (CA) inhibitory activities of newly synthesized quinazoline-linked benzensulfonamides 10-29, 31, 32, 35, 36, and 45-51 against human CA (hCA) isoforms I, II, IX, and XII were measured and compared to that of acetazolamide (AAZ) as a standard inhibitor. Potent selective inhibitory activity against hCA I was exerted by compounds 14, 15, 17, 19, 20, 21, 24, 25, 28, 29, 31, 35, 45, 47, 49, and 51 with inhibition constant (K I s) values of 39.4-354.7 nM that were nearly equivalent or even greater than that of AAZ (K I , 250.0 nM). Compounds 15, 20, 24, 28, 29, 45 and 47 proved to have inhibitory activities against hCA II with (K I s, 0.73-16.5 nM) that were similar or improved to that of AAZ (K I , 12.0 nM). Compounds 13-29, 31-32, and 45-51 displayed potent hCA IX inhibitory activities (K I s, 1.6-32.2 nM) that were more effective than or nearly equal to AAZ (K I , 25.0 nM). Compounds 14, 15, 20, 21, 26, 45, and 47 exerted potent hCA XII inhibitory activities (K I s, 5.2-9.2 nM), indicating similar CAI activities as compared to that of AAZ (K I , 5.7 nM).
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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