Carbonic anhydrases (CAs) catalyse the hydration of CO2 to bicarbonate at physiological pH. This chemical interconversion is crucial since HCO3- is the substrate for several biosynthetic reactions. This review is focused on the distribution and role of CA isoenzymes in both normal and pathological gastrointestinal (GI) tract tissues. It has been known for many years that CAs are widely present in the GI tract and play important roles in several physiological functions such as production of saliva, gastric acid, bile, and pancreatic juice as well as in absorption of salt and water in intestine. New information suggests that these enzymes participate in several processes that were not envisioned earlier. Especially, the recent reports on plasma membrane-bound isoenzymes IX and XII have raised considerable interest since they were reported to participate in cancer invasion and spread. They are induced by tumour hypoxia and may also play a role in von Hippel-Lindau (VHL)-mediated carcinogenesis.
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http://dx.doi.org/10.3748/wjg.v11.i2.155 | DOI Listing |
Biochemistry (Mosc)
December 2024
Medicinal Chemistry Center, Togliatti State University, Togliatti, 445020, Russia.
Human carbonic anhydrase IX (CAIX) plays a key role in maintaining pH homeostasis of malignant neoplasms, thus creating a favorable microenvironment for the growth, invasion, and metastasis of tumor cells. Recent studies have established that inhibition of CAIX expressed on the surface of tumor cells significantly increases the efficacy of classical chemotherapeutic agents and makes it possible to suppress the resistance of tumor cells to chemotherapy, as well as to increase their sensitivity to drugs (in particular, to reduce the required dose of cytostatic agents). In this work, we studied the ability of new CAIX inhibitors based on substituted 1,2,4-oxadiazole-containing primary aromatic sulfonamides, to potentiate the cytostatic effect of gefitinib (selective inhibitor of epidermal growth factor receptor tyrosine kinase domain) under hypoxic conditions.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, New Valley University, New Valley 72511, Egypt.
The present study aims to create spiro-N-(4-sulfamoyl-phenyl)-1,3,4-thiadiazole-2-carboxamide derivatives with anticancer activities. The in vitro anticancer evaluation showed that only the novel spiro-acenaphthylene tethered-[1,3,4]-thiadiazole (compound ) exhibited significant anticancer efficacy as a selective inhibitor of tumor-associated isoforms of carbonic anhydrase. Compound demonstrated considerable efficacy against the renal RXF393, colon HT29, and melanoma LOX IMVI cancer cell lines, with IC values of 7.
View Article and Find Full Text PDFMar Drugs
December 2024
Graduate Program in Biochemistry and Molecular Biology, Center of Biosciences, Federal University of Rio Grande do Norte-UFRN, Av. Sen. Salgado Filho, 3000, Natal 59078-900, Brazil.
Carrageenans have demonstrated enhanced antitumor activity upon depolymerization into disaccharides. However, the pharmacological viability of these disaccharides and their mechanisms of antitumor action remains to be fully elucidated. This study aimed to employ computational tools to investigate the pharmacological properties and molecular targets pertinent to cancer of the disaccharides derived from the primary carrageenans.
View Article and Find Full Text PDFInt J Nanomedicine
January 2025
College of Chemical and Material Engineering, Quzhou University, Quzhou, Zhejiang Province, 324000, People's Republic of China.
Background: Precise intraoperative tumor delineation is essential for successful surgical outcomes. However, conventional methods are often incompetent to provide intraoperative guidance due to lack specificity and sensitivity. Recently fluorescence-guided surgery for tumors to delineate between cancerous and healthy tissues has attracted widespread attention.
View Article and Find Full Text PDFRSC Med Chem
December 2024
VNU University of Education, Vietnam National University, Hanoi 144 Xuan Thuy, Cau Giay Ha Noi Vietnam.
Some novel sulphonyl thiourea derivatives (7a-m) containing 4,6-diarylpyrimidine rings were designed and synthesized using a one-pot procedure. These compounds exhibited remarkable dual inhibitory activity against human carbonic anhydrase CA I, CA II, CA IX, and XII isoenzymes and some cancer cell lines. Among them, some thioureas had significantly more potent inhibitory activities in the order of 7l > 7c > 7f (against the CA I isoform), 7f > 7b > 7c (against the CA II isoform), 7c > 7g > 7a > 7b (against the CA IX isoform), and 7d > 7c > 7g > 7f (against the CA XII isoform).
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