具有优秀抗肿瘤活性的香豆素杂合体

Coumarin Hybrids with Excellent Anticancer Activity

香豆素结构片段广泛存在于自然界中,其可修饰的位点较多,在新药研发领域有着广泛的应用。研究表明,香豆素类化合物可通过多种作用机制发挥抗肿瘤活性,故此类化合物具有良好的广谱体内外抗肿瘤活性。其中,Irosustat(STX64)具有良好的抗乳腺癌活性,目前正处于临床评价阶段,有望于不久的将来为人类健康服务。本文将介绍近年来所发现的具有优秀体内外抗肿瘤活性(半抑制浓度或50%生长抑制所需的药物浓度<10μmol/L或具有体内活性)的香豆素杂合体的最新研究进展,并总结了构-效关系和作用机制,为进一步研究提供理论支持。

The coumarin motif which is ubiquitous in nature is a highly privileged pharmacophore for the development of novel drugs.Coumarin derivatives can exert the anticancer activity through diverse antiproliferative mechanisms,so this kind of compounds possess promising broad-spectrum in vitro and in vivo anticancer activity.Moreover,the coumarin-based compound irosustat as the most emblematic example is under clinical trial for the treatment of breast cancer,revealing the potential of coumarin derivatives as putative anticancer drugs.This review focuses on the recent development of coumarin hybrids with IC50 or GI50 values in nanomolar or single-digit micromolar level or promising in vivo potency to facilitate the further rational design.