Potent Anticancer Activity with High Selectivity of a Chiral Palladium N-Heterocyclic Carbene Complex

Five enantiomeric pairs of palladium complexes of 1,2,4-triazole-derived chiral N-heterocyclic carbene ligands were investigated to probe the influence of chirality on the compound’s anticancer activity. Although no chirality-related influence was observed for any of the enantiomeric pair, strong anticancer activity was seen for a particular pair, (1S,2S,5R)-1c and (1R,2R,5S)-1c, which was significantly more active than the benchmark drug cisplatin for human breast cancer cells, MCF-7 (ca. 24–27-fold), and human cervical cancer cells, HeLa (ca. three- to fourfold). Broadening its scope of application, (1R,2R,5S)-1c also exhibited antiproliferative activity against lung cancer (A549), skin cancer (B16F10), and multidrug-resistant mammary tumor (EMT6/AR1) cell lines. Interestingly, (1R,2R,5S)-1c displayed 8- and 16-fold stronger antiproliferative activity toward B16F10 and MCF-7 relative to their respective noncancerous counterparts, L929 (fibroblast skin cells) and MCF10A (epithelial breast cells), thereby...