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

Abstract

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 (IC50=6.4 μm) and 2i against androgen‐responsive LNCaP cells (IC50=6.2 μm). In addition, 2c and 2h exhibited distinct activity in three cancer cell lines resistant to 1.

End Group Dye‐Labeled Polycarbonate Block Copolymers for Micellar (Immuno‐)Drug Delivery

“…The feasibility of this approach was first demonstrated by encapsulating the hydrophobic compound 3,3'-((3,4difluorophenyl)methylene)bis(1H-indole) (DIM-DF, Figure 3A). The anticancer drug DIM-DF was chosen as a model drug [40] due to its high log(P) value of 4.5 and its straightforward quantification by 19 F NMR. Formulations of DIM-DF were prepared by dropping a polymer-drug mixture in acetone of 10:1 polymer to drug (weight-to-weight ratio, 9.09 wt% drug) into water.…”

Indole‐3‐carbinol induces apoptosis in AGS cancer cells via mitochondrial pathway

“…Organometallic ferrocene derivatives 5a–c of DIM were synthesized as a continuation of this remarkable synthetic approach developed by Safe et al (2008), and they were evaluated against several tumor cell lines. In addition, 6a‐c demonstrated notable action against both androgen‐dependent (LNCaP) and androgen‐independent (C4‐2B, PC‐3) prostate cancer cells (Ahmad et al, 2019).…”

Studies on the mode of action of synthetic diindolylmethane derivatives against triple negative breast cancer cells

“…22 Three pentafluorophenyl derivatives of DIM were able to induce apoptosis in the pancreas, prostate, and breast cancer cells with significant GI50 values. 23 1,1-Bis(3-indolyl)-1-(p-substituted phenyl) methane (C-DIM) analogues act differentially on the orphan nuclear receptor, TR3/Nur77, inhibited cell cycle progression in G0/G1 to S-phase and induced apoptosis in lung cancer in vitro as well as in vivo conditions. 24 Nano lipid formulations of DIM derivatives improved the bioavailability and anticancer effects in cell lines and orthotopic models.…”

“…The DIM derivatives featuring indole moiety, 2‐methylindole moiety and 5‐ nitroindole moiety were shown to have growth inhibitory potential at a lower concentration than DIM when tested in pancreatic cancer, and triple negative breast cancer cells 22 . Three pentafluorophenyl derivatives of DIM were able to induce apoptosis in the pancreas, prostate, and breast cancer cells with significant GI50 values 23 . 1,1‐Bis(3‐indolyl)‐1‐( p ‐substituted phenyl) methane (C‐DIM) analogues act differentially on the orphan nuclear receptor, TR3/Nur77, inhibited cell cycle progression in G0/G1 to S‐phase and induced apoptosis in lung cancer in vitro as well as in vivo conditions 24 .…”