Chiral diaminocyclohexane coupling polyphenols: A new class of anticancer agents

Abstract

A new class of chiral diamine coupled polyphenols, compounds 3–8 were synthesized and tested against breast cancer (MCF-7), lung cancer (HBT-174, NCI-H460) and metastatic cancer cell lines (MDA-MB-453, MDA-MB-231 and MDA-MB-468). The results, based on SRB assay and colony formation assay, indicate that the compounds are selectively cytotoxic towards cancer cell-lines, and particularly towards metastatic cancer cell-lines. Gene expression studies by Real time RT-PCR demonstrated that compound 5 is an efficient regulator of antiapoptotic genes (Bcl-2) and cell cycle (cyclin D1) related genes. Moreover, compound 5 was evaluated using an isolated ALDH1-positive cell sub-population of metastatic MDA-MB-453 cells. In vitro mammosphere formation assay shows that this compound is highly inhibitory towards mammosphere formation and cell proliferation. These results indicate that the compounds investigated represent a class of effective and selectively toxic anticancer agents.