Novel sulfonamide-chalcone hybrid stimulates inflammation, angiogenesis and upregulates vascular endothelial growth factor (VEGF) in vivo.

Chalcones and sulfonamides are well-known chemical groups associated with several biological activities such as antibiotic, anti-inflammatory, and antitumor activities. Over the past few decades, a series of sulfonamide-chalcone hybrids have been synthesized and assessed to develop compounds with interesting biological properties for application in disease therapy. In the present study, a new sulfonamide-chalcone hybrid µ - (2,5-dichloro-N-{4-[(3E)-4-(3-nitrophenyl) buta-1,3-dien-2-yl] phenyl} benzene sulfonamide), or simply CL185, was synthesized, and its angiogenic activity was assessed using the chick embryo chorioallantoic membrane (CAM) assay at different concentrations (12.5, 25, and 50 µg/µL). To further investigate the role of CL185 in the angiogenic process, we evaluated the levels of vascular endothelial growth factor (VEGF) in all treated CAMs. The results showed that all concentrations of CL185 significantly increased tissue vascularization (p < 0.05) as well as the parameters associated with angiogenesis, in which inflammation was the most marked phenomenon observed. In all CAMs treated with CL185, VEGF levels were significantly higher than those in the negative control (p < 0.05), and at the highest concentration, VEGF levels were even higher than in the positive control (p < 0.05). The pronounced angiogenic activity displayed by CL185 may be related to the increase in VEGF levels that were stimulated by inflammatory processes observed in our study. Therefore, CL185 presents a favorable profile for the development of drugs that can be used in pro-angiogenic and tissue repair therapies.

New Synthetic Sulfonamide Chalcone Induced Cell Cycle Arrest and Cell Death in Colorectal Adenocarcinoma Metastatic Cells (SW-620).

BACKGROUND: New chalcones have been developed from the insertion of organic groups, among them sulfonamides, presenting varied biological activity. OBJECTIVE: The aim of this work was to determine the antitumor potential of a new synthetic sulfonamide chalcone (SSC185) against a colorectal metastatic lymph node-derived colorectal cancer cell line (SW-620). METHODS: Synthesis and characterization, including crystallography, of SSC185 were performed. SSC185 showed a selective cytotoxic effect against colorectal cancer cell lines. Therefore, the cytotoxic effect of SSC185 against SW- 620 was further investigated. We used optical and fluorescence microscopy, flow cytometry and Western blot to determine the antitumor effects of SSC185. RESULTS: SSC185 induced cytotoxicity in SW-620 cells in a time and concentration-dependent manner. Cell cycle progression was disrupted, with increased G2/M cell number and consequent cell death, with morphological alterations associated with apoptosis and necrosis. Cell death was associated with the activation and cleavage of PARP, and with reduced expression of the pro-apoptotic Bax protein and caspase 8, depending on the SSC185 concentration tested. Expression of the necroptosis pathway proteins RIP and MLKL was also reduced. These proteins are phosphorylated during the process of necroptosis. CONCLUSION: We suggest that the mechanism involved in the cytotoxic effect of SSC185 against SW-620 in vitro may be related to the induction of cell cycle arrest in the G2/M phase and cell death by apoptosis or necroptosis, depending on the concentration used.