Sulfonamide-chalcone hybrid compound suppresses cellular adhesion and migration: Experimental and computational insight

• DOI: 10.1016/j.cbi.2024.111115
• Publication Date: 2024-06-20T06:52:03Z
• Authors: Gisele Santos de ...; Andrea Felinto Moura; Ayslan Batista Ba...; Manoel Odorico Mo...; Claudia Pessoa; Caridad Noda Perez; Mirian Rita Carri...; Fábio de Oliveira...; Durcilene Alves d...; Paulo Sérgio de A...; Jefferson Almeida...; José Delano Barre...; Ana Jérsia Araujo
• Keywords: Sulfonamides; Melanoma, Experimental; Antineoplastic Agents; Microscopy, Atomic Force; Molecular Docking Simulation; Mice; Chalcone; Chalcones; Cell Movement; Cell Line, Tumor; Cell Adhesion; Animals; Matrix Metalloproteinase 2; Humans

In the present study, the effect of sulfonamide-chalcone 185 (SSC185) was investigated against B16-F10 metastatic melanoma cells aggressive actions, besides migration and adhesion processes, by in silico and in vitro assays. In silico studies were used to characterize the pharmacokinetic profile and possible targets of SSC185, using the pkCSM web server, and docking simulations with AutoDock Tools. Furthermore, the antimetastatic effect of SSC185 was investigated by in vitro experiments using MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide), colony, scratch, and cell adhesion assays, and atomic force microscopy (AFM). The molecular docking results show better affinity of SSC185 with the metalloproteinases-2 (MMP-2) and α5β1 integrin. SSC185 effectively restricts the formation of colonies, migration, and adhesion of B16-F10 metastatic melanoma cells. Through the AFM images changes in cells morphology was identified, with a decrease in the filopodia and increase in the average cellular roughness. The results obtained demonstrate the potential of this molecule in inhibit the primordial steps for metastasis, which is responsible for a worse prognosis of late stage cancer, being the main cause of morbidity among cancer patients.