title: Synthesis and biological evaluation of matrine derivatives containing benzo-α-pyrone structure as potent anti-lung cancer agents.
abstract: Matrine, an active component of root extracts from Sophora flavescens Ait, is the main chemical ingredient of Fufang Kushen injection which was approved by Chinese FDA (CFDA) in 1995 as an anticancer drug to treat non-small cell lung cancer and liver cancer in combination with other anticancer drugs. Owning to its druggable potential, matrine is considered as an ideal lead compound for modification. We delineate herein the synthesis and anticancer effects of 17 matrine derivatives bearing benzo-α-pyrone structures. The results of cell viability assays indicated that most of the target compounds showed improved anticancer effects. Further studies showed that compound 5i could potently inhibit lung cancer cell proliferation in vitro and in vivo with no obvious side effects. Moreover, compound 5i could induce G1 cell cycle arrest and autophagy in lung cancer cells through up-regulating P27, down-regulating CDK4 and cyclinD1 and attenuating PI3K/Akt/mTOR pathway. Suppression of autophagy attenuated 5i induced proliferation inhibition. Collectively, our results infer that matrine derivative 5i bears therapeutic potentials for lung cancer.
authors: School of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi 530004, PR China.
authors: Lichuan
authors: L
authors: Wu
authors: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors: Guizhen
authors: G
authors: Wang
authors: School of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi 530004, PR China.
authors: Shuaibing
authors: S
authors: Liu
authors: Guangxi Scientific Research Center of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi 530200, PR China.
authors: Jinrui
authors: J
authors: Wei
authors: School of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi 530004, PR China.
authors: Sen
authors: S
authors: Zhang
authors: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, People's Republic of China.
authors: Ming
authors: M
authors: Li
authors: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors: Guangbiao
authors: G
authors: Zhou
authors: School of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi 530004, PR China.
authors: Lisheng
authors: L
authors: Wang
mesh_terms: D000072283:A549 Cells; D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D011753:Pyrones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011807:Quinolizines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays; D000093842:Matrines
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D011753:Pyrones; D011807:Quinolizines; D000093842:Matrines