Pentafluorophenyl Substitution of Natural Di(indol-3-yl)methane Strongly Enhances Growth Inhibition and Apoptosis Induction in Various Cancer Cell Lines.

Di(indol-3-yl)methane (=3,3'-methanediyldi(1H-indole), DIM, 1) is a known weakly antitumoral compound formed by digestion of indole-3-carbinol (=1H-indol-3-ylmethanol), an ingredient of various Brassica vegetables. Out of a series of nine fluoroaryl derivatives of 1, three pentafluorophenyl derivatives 2c, 2h, and 2i were identified that exhibited a two to five times greater anti-proliferative effect and an increased apoptosis induction when compared with 1 in the following carcinoma cell lines: BxPC-3 pancreas, LNCaP prostate, C4-2B prostate, PC3 prostate and the triple-negative MDA-MB-231 breast carcinoma. Compound 2h was particularly efficacious against androgen-refractory C4-2B prostate cancer cells (IC =6.4 μm) and 2i against androgen-responsive LNCaP cells (IC =6.2 μm). In addition, 2c and 2h exhibited distinct activity in three cancer cell lines resistant to 1.