Chemopreventive flavonoids from Millettia pulchra Kurz var-laxior (Dunn) Z.Wei (Yulangsan) function as Michael reaction acceptors.

Natural NQO1 [NAD(P)H quinine oxidoreductase 1] inducing agents play a critical role in cancer chemoprevention. The expression of NQO1 is regulated by Michael reaction acceptors (MRAs) via the Keap1/Nrf2/ARE signaling pathway. The aims of this study were to identify and characterize novel effective chemopreventive agents from naturally occurring products. Using bioassay-guided isolation approaches 16 bioactive MRAs from Millettia pulchra Kurz var-laxior (Dunn) Z.Wei, also called Yulangsan as a famous Zhuang medicine. The structures were elucidated as chalcone (1-7), flavonone (8-14), flavanone (15) and isoflavan (16). Their electrophilic abilities and NQO1 inducing activity were assessed using GSH (glutathione) rapid screening, and in vitro cell-based (Hepa 1c1c7 cells) assay, respectively. Compounds 3, 4, 6, 13, and 14 showed to have NQO1 inducing activity. Among them, compounds 4 and 14 interact with NQO1 at Gly 149, Gly 150, Phe 106, Typ 105 and His 161, revealed by molecular docking studies.