Synthesis and evaluation of new 3-substituted-4-chloro-thioxanthone derivatives as potent anti-breast cancer agents

A series of 3-substituted-4-chloro-thioxanthones and their corresponding S,S-dioxidethioxanthone derivatives were designed and synthesized. The effects of our synthesized compounds on cell viability toward the MCF-7 and MDA-MB-468 breast cancer cell lines were evaluated. The most active compound was 4f, which was active against the MCF-7 and MDA-MB-468 cell lines with respective IC50 values of 7.2 and 3.9 μM. Interestingly, compound 4f did not impair cell viability of the cardiac myoblast H9C2 cell line (IC50 > 25 μM), indicating that this compound might not exhibit cytotoxic effects on the normal cardiac cells. Further, compounds 4b, 4f, 4j, 4s, 5b, 5f, 5j, and 5s were characterized by the NCI screening system. Results revealed that compounds 4f and 4s had effective anticancer activities against various cancer cell lines. Finally, our results indicated that the 3-substituted-4-chloro-thioxanthone derivatives have the potential to be further developed as promising small molecules for anticancer applications. Keywords: Thioxanthone, Thioxanthen-9-one-10,10-dioxide, MCF-7, MDA-MB-468, NCI 60-cell panel assay