新型Combretastatin A-4衍生物的合成及生物活性研究

Synthesis and Biological Activities of Novel Combretastatin A-4 Derivatives

Combretastatin A-4是一类结构独特的天然产物,具有较好的抗肿瘤活性。为了进一步研究该类化合物的构效关系,以3,4,5-三甲氧基苯甲醛和3-羟基-4-甲氧基苯乙酸为原料,在碱性条件下经缩合、酰化反应合成了5个未见文献报道的Combretastatin A-4衍生物。并通过1HNMR、13CNMR和MS对其结构进行确证。采用MTT法对合成的目标产物体外抗肿瘤活性进行了初步测定。结果表明,(E)-N-(2-(二甲氨基)乙基)-2-(3-羟基-4-甲氧基苯基)-3-(3,4,5-三甲氧基苯基)丙烯酰胺和(E)-2-(3-羟基-4-甲氧基苯基)-N-(2-(吡咯烷-1-基)乙基)-3-(3,4,5-三甲氧基苯基)丙烯酰胺对K562肿瘤细胞有较弱的抑制作用。

Combretastatin A-4 is natural product with unique structure which has excellent antitumor activity.To investigate the structure-activity relationship of Combretastatin A-4,we synthesized 5 novel combretastatin A-4 derivatives through condensation reaction and acylation under alkaline condition with 3,4,5-trimethoxybenzaldehyde and 3-hydroxy-4-methoxyphenylacetic acid as substrates.The compounds were characterized by 1HNMR,13CNMR and MS.The preliminary in vitro MTT assay indicated that(E)-N-(2-(dimethylamino)ethyl)-2-(3-hydroxy-4-methoxyphenyl)-3-(3,4,5-trimethoxyphenyl)acrylamide and(E)-2-(3-hydroxy-4-methoxyphenyl)-N-(2-(pyrrolidin-1-yl)ethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide had weak antitumor activity against K562 tumor cell line.