Novel Sulfonamide Derivatives: Proliferation and Migration in MCF‑7 Cells under Normoxia and Hypoxia

Abstract

Hypoxia is a recognised characteristic of the tumour microenvironment and significantly contributes to therapeutic resistance and aggressive behaviour in breast cancer. Carbonic anhydrase IX (CA IX) is an enzyme induced by hypoxia and is important for maintaining pH homeostasis, thereby enabling cancer cell survival in low-oxygen environments. Sulfonamide-based compounds are known to act as selective CA IX inhibitors, offering therapeutic promise especially under hypoxic stress. The purpose of this study was to elucidate the effects of newly synthesised sulfonamide derivatives on the viability and migration of the breast cancer cell line MCF-7 under normoxic and chemically induced hypoxic conditions (150 µM cobalt chloride). The compounds were synthesised via standard sulfonamide coupling reactions, purified, and characterised using spectroscopic techniques. Cytotoxicity was assessed through the MTT assay, while the scratch assay was utilised to measure the compounds' effect on cell migration. Results showed that the sulfonamide derivatives (compounds 3b, 3d-g) demonstrated a significant dose-dependent reduction in cell viability in the MCF-7 cell line, with greater inhibition under hypoxic conditions. Moreover, migration was notably suppressed in hypoxia-treated cells, indicating impaired cellular motility upon CA IX inhibition. These findings suggest that the synthesised sulfonamide derivatives may act by targeting both proliferation and migration mechanisms under hypoxia. Their efficacy in the luminal breast cancer model positions them as promising candidates for further development. Additional molecular assays, including qPCR and protein expression studies, are recommended to further elucidate their mechanisms.