Design, Synthesis And Biological Activity Study Of New Sinapyl Alcohol Derivaties, Neolignans And Its Nitrogen-containing Analogues

Natural products play an important role in drug discovery for their structural and biological diversities. It's an important approach to develop new antitumor agents by synthesis and structural modification of the active natural product as the lead compound. Phenylpropanoids, widespread in nature, have broad and interesting bioactivies and this thesis is carried out on two kinds of natural phenylpropanoids.The first part of the thesis is design, synthesis and SAR of new sinapyl alcohol derivatives and its analogues including three series of compounds. We have the first serie as sinapyl alcohol derivatives with 7-geranyl sinapyl alcohol as our lead compound isolated from Ligularia nelumbifolia. Four kinds of derivatives including substituted sinapic acid ethyl esters, sinapic acids, sinapyl alcohols and sinapyl aldehydes were synthesized and subjected to six human tumor cell lines screening. The results indicate that some of the synthetic compounds possess remakable cytotoxicties on selected tumor cell lines with IC₅₀ values at 10^-6 M scale. With the cytotoxicitic results, SAR studies were performed and a 3D-QSAR model was built by the preliminary CoMFA molecular-modelling study, which could be a guide for further drug design. Another two series of compounds as mono-, double- substituted sinapl alcohols and the conjugated diene derivatives were also synthesized and their biological activities assay is still in progress.The second part is based on our former research results and reported curcumin and caffeic acid phenylester, the representative of cytotoxic neolignans. Three series of neolignans and its nitrogen-containing analogues were designed and synthesized by coupling the two parts of substitutied sinapic acids and subsititued sinapyl alcohols or substituted amines. The three series are distinguished as substituted sinapic acid sinapyl esters, substituted cinnamamide derivatives and phenylamine acetyl sinapic acid ester derivatives and their biological activities assay is still in progress.