Design and synthesis of novel 4-thiazolidinone derivatives with promising anti-breast cancer activity: Synthesis, characterization, in vitro and in vivo results

Abstract

Novel lead compounds as anticancer agents with the ability to circumvent emerging drug resistance have recently gained a great deal of interest. Thiazolidinones are among such compounds with well-established biological activity in the field of oncology. Here, we designed, synthesized and characterized a series of thiazolidinone structures (8a-8k). The results of anti-proliferative assay led to the discovery of compound 8j with a high potent cytotoxic effect using colon, liver and breast cancer cells. Furthermore, MDA-MB-231 and 4T1 cell lines were used to represent triple negative breast cancer (TNBC). Next, a number of in vitro and in vivo evaluations were carried out to demonstrate the potential activity against TNBC and also elucidate the possible mechanism of cell death induction. Our in vitro outcomes exhibited an impressive anticancer activity for compound 8j toward MDA-MB-231 cells through inducing apoptosis and a remarkable anti-metastatic feature via suppressing MMP-9 expression as well. Consistently, the in vivo and immunohistopathologic evaluations demonstrated that this compound significantly inhibited the 4T1 induced tumor growth and its metastasis to the lung. Altogether, among numerous thiazolidinone derivatives, compound 8j might represent a promising anticancer agent for TNBC, which is a major concern in the developed and developing countries.

Keywords: Apoptosis; BALB/c; Metastasis; TNBC; Thiazolidinone.