Carbonic anhydrase inhibitors. Synthesis, and molecular structure of novel series N-substituted N′-(2-arylmethylthio-4-chloro-5-methylbenzenesulfonyl)guanidines and their inhibition of human cytosolic isozymes I and II and the transmembrane tumor-associated isozymes IX and XII

Some N-(5-methyl-1,3,4-thiadiazol-2-yl)-4-[(3-substituted) ureido/thioureido]benzenesulfonamides as carbonic anhydrase I and II inhibitors

“…Physicochemical and spectroscopic characterization of the urea and thiourea derivatives have been previously described. The structures of the compounds (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) were confirmed by IR, 1 H-NMR, MS and elemental analysis. IR spectra of the compounds (1-14) afforded urea/ thiourea and sulfonamide N-H streching 3374-3102cm-1 and C=O streching 1692-1651cm-1 bands and aromatic rings' C-H streching 3096-3011cm-1 bands.…”

“…Among these subtypes the CA IX and XII are highly secreted in some tumors and mostly associated with oncogenesis (13). The previous studies have also indicated that the CA I and II levels were also higher in several cancer types, such as higher cytosolic erythrocte levels in stomach, prostate, lung and ovary tumors; also in hematological diseases such as leukemia (14).…”

Carbonic anhydrase inhibitors: guaiacol and catechol derivatives effectively inhibit certain human carbonic anhydrase isoenzymes (hCA I, II, IX and XII)

“…Indeed, the expression level of hCA IX was elevated in response to hypoxia, which is a consequence of the rapid growth of many tumours. The general result of hCA IX overexpression in tumours is a pH decrease in the extracellular micro-environment from pH 7.4 (normal tissue) to 6.8 (hypoxic tumour), which promotes tumour cell survival and invasion 2,85 . Considering the abnormally high-expression of CA IX in many hypoxic tumours and its demonstrated role in the tumour acidification processes and oncogenesis, this isoform constitutes an attractive target for anticancer therapy 86 .…”

Synthesis of some natural sulphonamide derivatives as carbonic anhydrase inhibitors

“…17,22 Primary sulphonamides are well known carbonic anhydrase inhibitors, first examples of which were derivatives of clinically used ones such as acetazolamide (AAZ), ethoxzolamide (EZA) and indisulfam (IND) (Figure 1.). 23 Today, it is acknowledged that when designing therapeutic agents, selective inhibition of CAs or, at least, organ specific targeting is the main goal. 15 However, since there are at least fifteen carbonic anhydrase isozyme in human, their spread localization in many tissues and organs, and none of the currently sulphonamide or sulfamate CA inhibitors in clinical use is selective for a specific isozyme is a high barrier to achieve.…”

“…[15][16][17][18] Carbonic anhydrases play crucial roles in a variety of physiological processes such as electrolyte secretion in a variety of tissues and organs, calcification, biosynthetic reactions (lipogenesis, ureagenesis, and gluconeogenesis are among them), pH and CO 2 homeostasis, bone resorption and tumorigenicity, and many others. [21][22][23] Inhibition of carbonic anhydrases are becoming increasingly popular as a research subject, which is due to their abnormal levels associated with various diseases such as glaucoma, cancer, osteoporosis and some neurological disorders. 15 Sulphonamides, phenols and coumarins are three examples of CA inhibitors acting through different mechanisms, (i) displacing zinc-bound water/hydroxide ion by coordination to the Zn(II) ion in the enzyme active side and leading to a tetrahedral geometry, or by addition to the metal coordination sphere and leading to a trigonal bipyramidal geometry, (ii) hooking up to the Zn(II)-bound water/hydroxide ion and (iii) by obstructing the active site cavity of the enzyme, respectively.…”