Synthesis and Computational Studies on Indole Sulfonamide Derivatives a New Class of Anti breast cancer agents

Abstract

Breast cancer is the most common cause of cancer-related death in women. Derivatives of either of indole or sulfonamide are currently marketed as successful anticancer agents, such as vincristine and belinostat, respectively. Accordingly, our aim was to explore novel indole-sulfonamide hybrid derivatives for activity against breast cancer. Therefore, we synthesized and biologically evaluated the most promising indole-sulfonamide derivatives against human breast cancer cell line (MCF7-9D). Additionally, the synthesized compounds were docked to the active site of multi-target proteins: tyrosine kinase receptor (5JFV, 4H1M, 3FZO and 5TTU), HIV-1 (1HHJ and 5UY3) and pyrovate dehydrogenase kinase (1Y8N) using the docking program Molegro virtual docker. Finally, drug-likeness, bioavailability, topological polar surface area, percentage of absorption and aqueous solubility of these compounds were estimated in silico by Molinspiration software. At a dose of 100g/ml, the synthesized compounds (4a-4e) showed significant anticancer activity against MCF7-9D (% inhibition ranged from 63 to73.5 %). These compounds showed high docking score and binding energy to the selected protein targets, which were in good agreement with the observed anticancer activity. The predicted physicochemical properties of these compounds indicate good drug-like properties and adequate oral bioavailability. In conclusion, our results suggest that these new indole-sulfonamide hybrid derivatives could be a promising new drug class for breast cancer.