Chiral Salicyl Diamines: Potent Anticancer Molecules

A set of 12 enantiomeric diamine‐based small molecules was synthesized and screened for anticancer activity against five human cancer cell lines: NCI‐H460, A549, MCF‐7, SK‐BR‐3, and T‐47D. The salicyl diamino compounds (1–6) were found to induce inhibition of the growth of cancer cells at submicromolar concentrations. The lead compound, N,N′‐bis‐salicyl‐(1R,2R)‐diaminocyclohexane (1) displayed single‐reagent anticancer activity with an IC50 value equal to or less than 2.0 μM in H460 and A‐549 cancer cells. SRB and colony formation assays indicated that compound 1 shows greater cytotoxic activity toward MCF‐7 cells than MCF‐10A cells. Real‐time RT‐PCR analysis demonstrated that compound 1, is an extremely efficient regulator of antiapoptotic genes, Bcl‐xL, Bcl‐2, and the cell cycle related gene, cyclin D1. This study provides a new insight into the development of novel small molecules in the treatment of human breast cancers. A grand challenge for chemical biologists involves the identification of small molecules that can effectively manipulate the transcription of encoded genes in cancer cells. Chiral N,N′‐bis‐salicyl diamino compounds have now been identified as an effective anticancer agent in the downregulation of Bcl‐2 family gene expression in human breast cancer cells.