Synthesis and the In Vitro Evaluation of Antitumor Activity of Novel Thiobenzanilides

Abstract

Cancer is a generic term for a large group of diseases that are the second-leading cause of death worldwide, accounting for nearly 10 million deaths in 2020. Melanoma is a highly aggressive skin tumor with an increasing incidence and poor prognosis in the metastatic stage. Breast cancer still stands as one of the major cancer-associated deaths among women, and diagnosed cases are increasing year after year worldwide. Despite the recent therapeutic advances for this type of cancer, novel drugs and treatment strategies are still urgently needed. In this paper, the synthesis of 18 thiobenzanilide derivatives (17 of them new) is described, and their cytotoxic potential against melanoma cells (A375) and hormone-dependent breast cancer (MCF-7) cells is evaluated using the MTT assay. In the A375 cell line, most of the tested thiobenzanilides derivatives showed EC50 values in the order of μM. Compound 17 was the most promising, with an EC50 (24 h) of 11.8 μM. Compounds 8 and 9 are also interesting compounds that deserve to be further improved. The MCF-7 cell line, on the other hand, was seen to be less susceptible to these thiobenzanilides indicating that these compounds show different selectivity towards skin and breast cancer cells. Compound 15 showed the highest cytotoxic potential for MCF-7 cells, with an EC50 (24 h) of 43 μM, a value within the range of the EC50 value determined for tamoxifen (30.0 μM). ADME predictions confirm the potential of the best compounds. Overall, this work discloses a new set of thiobenzanilides that are worth being considered as new scaffolds for the further development of anticancer agents.