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: Lichuan Wu, Guizhen Wang, Shuaibing Liu, Jinrui Wei, Sen Zhang, Ming Li, Guangbiao Zhou, Lisheng Wang
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 35918 (10 27 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 27786281 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkaloids
• Antineoplastic Agents
• Pyrones
• Quinolizines
• Matrines

Topics

• A549 Cells
• Alkaloids (chemical synthesis, chemistry, pharmacology)
• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Autophagy (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Drug Discovery
• Drug Evaluation, Preclinical
• G1 Phase Cell Cycle Checkpoints (drug effects)
• Humans
• Lung Neoplasms (drug therapy, metabolism, pathology)
• Mice
• Mice, SCID
• Pyrones (chemical synthesis, chemistry, pharmacology)
• Quinolizines (chemical synthesis, chemistry, pharmacology)
• Signal Transduction (drug effects)
• Tumor Stem Cell Assay
• Xenograft Model Antitumor Assays
• Matrines