靛红杂合体抗肿瘤活性研究的最新进展(2018—2022)

Isatin Hybrids as Promising Anticancer Agents: An up-to-date Overview(2018—2022)

靛红母核可供修饰的位点较多,可引入多种官能团和药效团。靛红具有多种生物活性,是新药研发中常见的药效团。研究表明,靛红衍生物可通过抑制组蛋白脱乙酰酶、碳酸酐酶、酪氨酸激酶和微管蛋白等作用机制阻滞肿瘤细胞周期、诱导细胞凋亡。因此,靛红类化合物具有潜在的抗肿瘤活性。其中,靛红杂合体具有同时与多个作用靶点相结合的潜力,在提高药效、克服耐药性和降低毒副作用方面具有一定的优势。值得一提的是,多个靛红杂合体如靛红—吡咯杂合体舒尼替尼和司马沙尼等已用于临床治疗各种癌症或正处于临床评价阶段,提示靛红杂合体在抗肿瘤领域具有广泛的应用前景。本文将着重介绍2018—2022年间所发展的具有抗肿瘤活性的靛红杂合体的最新研究进展,为进一步研究提供参考。

Almost all positions of isatin skeleton can be modified, and various functional groups and pharmacophores can be incorporated into isatin moiety. Isatin possesses diverse biological activities and play a prominent role in the discovery of new drugs. Mechanistically, isatin derivatives could arrest cancer cell cycle and induce apoptosis through a variety of mechanisms such as inhibition of histone deacetylase, carbonic anhydrase,tyrosine kinase and tubulin. Hence, isatin derivatives are useful scaffolds for the development of novel anticancer agents. Isatin hybrids have the potential to act on multiple targets simultaneously, and consequently, isatin hybrids could improve efficacy, overcome drug resistance and reduce side effects. In particular, several isatin hybrids like isatin-pyrrole hybrids sunitinib and semaxanib have already been applied in the clinical treatment of various cancers or are in the clinical evaluations, demonstrating that isatin hybrids have a broad application prospect in the anticancer field. This review covers the recent advances in isatin hybrids with potential anticancer activity to set up the direction for the design and development of isatin hybrids with high efficiency and low toxicity.