الفهرس | Only 14 pages are availabe for public view |
Abstract Human carbonic anhydrase (hCA) is a crucial zinc-containing metalloenzyme that catalyzes the reversible hydration process of carbon dioxide to bicarbonate ion and proton which is important for several physiological and pathological processes. The hCA consists of 15 different isoforms that vary in terms of their molecular features, cellular locations, organ and tissue distribution, and expression levels. Consequently, hCA inhibitors (hCAIs) have become an important class of treatments of diseases such as glaucoma, cancer, and others based on isoforms cellular distribution. The cytosolic hCA isoforms I and II (hCA I and II) are highly abundant in red blood cells, underscoring their potential impact on the pharmacokinetics of drugs. Also, the presence of hCA II has been investigated in the eye, such isoform is a promising target for the development of hCAIs with the antiglaucoma effect. The transmembrane hCA isoforms such as hCA IX and hCA XII have shown increased expression in hypoxia-induced tumor cells thus, such isoforms are promising targets for the development of hCAIs with anticancer activity. Herein, we describe the design and synthesis of thirty-four compounds of two series of novel derivatives; twenty aryl pyrimidine benzenesulfonamides (APBSs) 5a-n, 6a-c, 7a,b, and 8 and fourteen coumarin-based thiazoles (CBTs) 13a-h, 14, and 15a-e to explore new potent and selective anticancer agents towards the hCA IX. The structures of the synthesized compounds were confirmed using 1H NMR, 13C NMR, single crystal X ray, IR, mass spectroscopy, elemental analysis for certain atoms, and HPLC. A single crystal X-ray analysis was performed for the representative compound (CBT-13e) to determine the geometrical isomerism (E or Z). Accordingly, compound CBT-13e exists in the E-isomer (deposition number CCDC 2298601). |