Effective Anticancer Potential of a New Sulfonamide as a Carbonic Anhydrase IX Inhibitor Against Aggressive Tumors

This study examines efficiency of a newly synthesized sulfonamide derivative 2-bromo-N-(4-sulfamoylphenyl)propanamide (MMH-1) on the inhibition of Carbonic Anhydrase IX, which is overexpressed in many solid tumors including breast cancer. The inhibitory potential of MMH-1 compound against hCA I, II, IX, and XII, was evaluated. To this context, the cytotoxic effect of MMH-1 on cancer and normal cells was tested and found to selectively affect MDA-MB-231 cells. MMH-1 reduced cell proliferation by holding cells in the G0/G1 phase (72%) and slowed the cells' wound healing capacity. MMH-1 inhibited CA IX under both hypoxic and normoxic conditions and altered the morphology of triple negative breast cancer cells. In MDA-MB-231 cells, inhibition of CA IX was accompanied by a decrease in extracellular pH acidity (7.2), disruption of mitochondrial membrane integrity (80%), an increase in reactive oxygen levels (25%), and the triggering of apoptosis (40%). In addition, the caspase cascade was activated in MDA-MB-231 cells, triggering both the extrinsic and intrinsic apoptotic pathways. TThese results propose that the MMH-1 compound could triggers apoptosis in MDA-MB-231 cells via the pH/MMP/ROS pathway through the inhibition of CA IX. This compound is thought to have high potential and promising anticancer properties in the treatment of aggressive tumors.PMID:38323458 | DOI:10.1002/cmdc.202300680
Source: ChemMedChem - Category: Chemistry Authors: Source Type: research