Synthesis Of 14-Substituted Matrine Derivatives And Their Activities In Anti-Tumor

Matrine is one kind of active ingredients of traditional Chinese medicine, with extensive pharmacological activities. It has important application value in the central nervous system, cardiovascular system, digestive system et al. Matrine has significant inhibitory effect on the tumor, liver cancer et al. Although matrine has many pharmacological functions and biological activity, the matrine has low bioavailability and toxic side effects, these shortcomings limit its application in the clinical.Quinoline, benzene and 2,4-dioxane, naphthalene ring, indoles material has good pharmacological activities, and have significant in antitumor activity.We designed and synthesized nineteen novel matrine derivatives base on the principle of Drug split by introducing nitrogen-containing heterocycle, oxygen-containing heterocyclic and naphthalene ring. We expecte they can create synergies, thereby improving the pharmacological activity of matrine. The nineteen matrine derivatives carried out molecular docking simulation by using computer simulation system, Through the simulation data, we can predict its pharmacological activity. The structure of 14-substituted matrine derivatives were characterizated and confirmed by nuclear magnetic resonance (NMR), mass spectrometry (MS) and infrared spectroscopy (IR).Matrine derivatives anti-tumor activity in vitro test results show that compared with matrine, except YF-4 inhibitory activity on A549 and HepG2, YF-6 and YF-12 inhibition activity on A549 than matrine’s lower, remaining matrine derivatives showed a good anti-tumor activity., and further results indicated that YF-8 exerted its anti-proliferation activity by induction of apoptosis and oxidative stress in cancer cells, as well as arrest of cell cycle of cancer cells in Gl phase.Later, we conducted docking simulations between YF-8 with cell cycle regulation target and apoptosis target, respectively. Docking results show that the formation of van der Waals forces between YF-8 and CDK2, electrostatic interaction, hydrophobic interaction and hydrogen bonds, which can make the compounds closely integrated with the target, thereby inhibiting its activity.