含香豆素结构的1,4-戊二烯-3-酮类衍生物的合成及生物活性

Synthesis and Bioactivities of Penta-1,4-dien-3-one Derivatives Containing a Coumarin Moiety

为了开发新型抗肿瘤药物候选分子,将香豆素单元有机融入1,4-戊二烯-3-酮分子骨架中,设计合成了16个结构新颖的单羰基姜黄素衍生物.在确证目标分子结构后,采用甲基四氮唑盐(MTT)比色法测试了其对胃癌SGC7901细胞和肝癌HepG2细胞体外增殖的抑制活性.生物活性测试结果表明,绝大多数目标分子均能显著抑制SGC7901和HepG2细胞的体外增殖.其中,化合物4c和4j对SGC7901细胞的半数抑制浓度(IC_(50))为0.22和0.27μmol/L,其活性显著优于对照药剂表柔比星(1.23μmol/L).同时,化合物4l对HepG2细胞的IC_(50)值(0.47μmol/L)也显著优于表柔比星(2.30μmol/L).细胞形态学研究结果进一步证实,含香豆素结构1,4-戊二烯-3-酮衍生物能显著抑制多种肿瘤细胞的体外增殖,可作为高效抗肿瘤药物候选分子进行深度开发.

Aiming to develop novel candidates for antitumor drugs,sixteen monocarbonyl curcumin derivatives were constructed by dexterously intergrating a coumarin fragment into the penta-1,4-dien-3-one skeleton deriving from the structural optimization of a curcumin molecule.After structural confirmations,the above derivatives were tested by a methyl thiazolyl tetrazolium(MTT)colorimetric assay for their inhibitory activities against the in vitro proliferation of gastric cancer cells(SGC7901)and hepatoma carcinoma cells(HepG2).The bioassay results demonstrated that most of synthesized molecules exhibited outstanding inhibitory effects against the in vitro proliferation of SGC7901 and HepG2 cells.Strikingly,the half maximal inhibitory concentrations(IC_(50))of compounds 4c and 4j against SGC7901 cells reached 0.22 and 0.27μmol/L,respectively,which are obviously better than that of epirubicin(1.23μmol/L).Meanwhile,the IC_(50) value of compounds 4l against HepG2 cells reached 0.47μmol/L that is observably superior to that of epirubicin(2.30μmol/L).Subsequently,morphological observations reconfirmed the outstanding advantage of coumarin-containing penta-1,4-dien-3-ones on inhibiting the in vitro proliferation of tumor cells,which implied these distinctive derivatives could be further developed as novel candidates for antitumor drugs.