Design, Synthesis, and Biological Evaluation of Marchantin C-NO Donor Hybrids for Overcoming Pgp-Mediated Drug Resistance by Targeting Lysosome.

A series of marchantin C-NO donor hybrids were designed, synthesized, and evaluated for their antitumor activity and . Notably, MC-furoxan hybrid exhibited the best selective inhibitory activity against MCF-7/ADR (IC = 0.024 μM) with 883 times potency compared with MCF-7 cells (IC = 21.

Discovery of potent quinone oxidoreductase 2 inhibitors to overcome TRAIL resistance of non-small cell lung cancer.

Resistance to tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) of cancer cells is a main obstacle for the chemotherapy. NRH: quinone oxidoreductase 2 (NQO2), known as a chemopreventive target, has emerged as a promising therapeutic target for overcoming TRAIL resistance in non-small cell lung cancer (NSCLC). Here we report the design, synthesis and evaluation of resveratrol analogues as novel selective NQO2 inhibitors, and analogue 20b, with potent NQO2 inhibitory activity (IC = 95 nM) and relatively low cytotoxicity, displayed synergistic lethal effects in combination with TRAIL on TRAIL-resistant NSCLC cells.