title: Chemopreventive flavonoids from Millettia pulchra Kurz var-laxior (Dunn) Z.Wei (Yulangsan) function as Michael reaction acceptors.
abstract: 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.
authors: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, Wenhua Road 103, Shenyang 110016, PR China.
authors: Wenli
authors: W
authors: Wang
authors: Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, Wenhua Road 103, Shenyang 110016, PR China; School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors: Jian
authors: J
authors: Wang
authors: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, Wenhua Road 103, Shenyang 110016, PR China. Electronic address: liningsypharm@163.com.
authors: Ning
authors: N
authors: Li
authors: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors: Xiangrong
authors: X
authors: Zhang
authors: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, Wenhua Road 103, Shenyang 110016, PR China.
authors: Weihong
authors: W
authors: Zhao
authors: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, Wenhua Road 103, Shenyang 110016, PR China.
authors: Jiayuan
authors: J
authors: Li
authors: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, Wenhua Road 103, Shenyang 110016, PR China.
authors: Yingying
authors: Y
authors: Si
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects*; D005419:Flavonoids / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D033641:Millettia / Q000737:chemistry*; D062105:Molecular Docking Simulation; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*
chemical_list: D016588:Anticarcinogenic Agents; D005419:Flavonoids; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; C491732:Nqo1 protein, mouse
keywords: Cancer chemoprevention; Flavonoids; Millettia pulchra Kurz var-laxior (Dunn) Z.Wei; Molecular docking; NQO1; Yulangsan