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

Wenli Wang; Jian Wang; Ning Li; Xiangrong Zhang; Weihong Zhao; Jiayuan Li; Yingying Si

doi:10.1016/j.bmcl.2015.01.009

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

Bioorg Med Chem Lett. 2015 Mar 1;25(5):1078-81. doi: 10.1016/j.bmcl.2015.01.009. Epub 2015 Jan 13.

Authors

Wenli Wang¹, Jian Wang², Ning Li³, Xiangrong Zhang⁴, Weihong Zhao¹, Jiayuan Li¹, Yingying Si¹

Affiliations

¹ 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.
² 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.
³ 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.
⁴ School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, PR China.

PMID: 25630222
DOI: 10.1016/j.bmcl.2015.01.009

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.

Keywords: Cancer chemoprevention; Flavonoids; Millettia pulchra Kurz var-laxior (Dunn) Z.Wei; Molecular docking; NQO1; Yulangsan.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anticarcinogenic Agents / chemistry*
Anticarcinogenic Agents / isolation & purification
Anticarcinogenic Agents / pharmacology*
Cell Line, Tumor
Enzyme Activation / drug effects*
Flavonoids / chemistry*
Flavonoids / isolation & purification
Flavonoids / pharmacology*
Humans
Mice
Millettia / chemistry*
Molecular Docking Simulation
NAD(P)H Dehydrogenase (Quinone) / metabolism*

Substances

Anticarcinogenic Agents
Flavonoids
NAD(P)H Dehydrogenase (Quinone)
NQO1 protein, human
Nqo1 protein, mouse