Synthesis And Study Of Biological Activity Of Sampangine Derivatives

Sampangine(C15H8N2O)which was widely distributed in annonaceae plants is one of azaoxoaporphine alkaloids.Plant-derived sampangine alkaloid shows broad and potent antibacterial,antifungal,antimalarial,anti-inflammatory,antiparasitic and antitumor activities.These made it a hot research.However,its toxicity and poor water solubility and the scarcity from the natural source have limited its development and application.Further structural modification appeared to be necessary for better promotion of the application of the sampangine.The main contents are as follows.1.Five sampangine derivatives 2-6 had been designed and synthesized.All the new derivatives were confirmed by 1H NMR,13C NMR and HRMS.The in vitro antitumor activity of sampangine and its derivatives against SK-OV-3,Hep-G2,NCI-H460,A549,MGC-803,Hela and HL-7702 cell lines were tested by MTT method.All the compounds exhibited different inhibitory activity adainst the tumor cells mentioned above.The sampangine 1 and compound 6 exhibited higher inhibitory activity against human ovarian cancer cell lines.Experimental results showed that significant apoptotic phenomenon was occurred when SK-OV-3 cells were treated with the sampangine 1 and compound 6 respectively.The rate of apoptosis was concentration-dependent manner.2.The sampangine 1 could inhibit the breaking of DNA single strand mediated by Topo I at 20 ?M by DNA agarose gel electrophoresis analysis.The breaking activity of Topo I on the double stranded helical DNA was also inhibited similarly at the same drug concentration.Furthermore,compound 6 exhibited the similar activity with lower concentration(10 ?M).Compounds 2-5 have no effect on Topo I regardless concentration.3.The minimum inhibitory concentration(MIC)of the compounds toward Micrococcus luteus,Candida albicanb,Staphylococcus aureus,Bacillus subtilis,Escherichia coli,Bacillus cereus and Dysentery bacillus was assessed by double-dilution method doubling dilution.Antibacterial experiment showed that all compounds exhibited different inhibitory potency toward all tested bacteria.Sampangine 1 and the compound 6 exhibited stronger inhibitory potency toward Bacillus cereus and Dysentery than ampicillin sodium.Furthermore,sampangine 1 and the compound 6 had strong bactericidal effect on Bacillus cereus and Dysentery.