Xu Zhi, Li Rongqiang, Ding Kexin, Wang Yiling, Zhuang Yafei
Huanghuai University Industry Innovation & Research and Development Institute, Huanghuai University, Zhumadian, Henan, China.
School of Chemistry and Pharmaceutical Engineering, Huanghuai University, Zhumadian, Henan, China.
Future Med Chem. 2025 May;17(10):1155-1173. doi: 10.1080/17568919.2025.2504336. Epub 2025 May 14.
Cancer can invade and destroy any part of the body, representing a grand social, public health, and economic challenge. Chemotherapy plays a crucial role in cancer treatment, and in recent decades, hundreds of anticancer chemotherapeutics have been introduced. Nevertheless, multidrug resistance and side effects are the main obstacles to successful cancer therapy, highlighting the pressing requirement for the development of new chemotherapeutics to address the above issues. Indole hybrids not only have the potential to surmount drug resistance and adverse effects caused by individual components but also can enhance efficacy and improve pharmacokinetic characteristics since hybrid molecules can concurrently regulate multiple targets within cancer cells. Moreover, numerous indole hybrids exemplified by mobocertinib (indole-pyrimidine hybrid) and osimertinib (indole-quinazoline hybrid) have already been utilized in clinical cancer treatment. Therefore, indole hybrids have emerged as valuable scaffolds for the treatment and eradication of cancer. This review aims to elucidate the current landscape of indole-(fused) pyri(mi)dine hybrids, including indole-quinolines/quinolinones, indole-pyridines, indole-pyrimidines, and indole-fused pyrimidines, with antitumor therapeutic potential, offering effective candidates for in-depth preclinical evaluations, encompassing articles published from 2021 onward.
癌症能够侵袭并破坏身体的任何部位，这是一项重大的社会、公共卫生和经济挑战。化疗在癌症治疗中起着关键作用，近几十年来，已有数百种抗癌化疗药物问世。然而，多药耐药性和副作用是癌症治疗取得成功的主要障碍，这凸显了开发新的化疗药物以解决上述问题的迫切需求。吲哚杂化物不仅有可能克服单个成分引起的耐药性和不良反应，而且由于杂化分子可以同时调节癌细胞内的多个靶点，还能够增强疗效并改善药代动力学特性。此外，以莫博替尼（吲哚 - 嘧啶杂化物）和奥希替尼（吲哚 - 喹唑啉杂化物）为代表的众多吲哚杂化物已被用于临床癌症治疗。因此，吲哚杂化物已成为治疗和根除癌症的有价值的骨架。本综述旨在阐明吲哚 -（稠合）吡啶（嘧啶）杂化物的当前研究状况，包括吲哚 - 喹啉/喹啉酮、吲哚 - 吡啶、吲哚 - 嘧啶和吲哚稠合嘧啶，这些具有抗肿瘤治疗潜力，为深入的临床前评估提供有效的候选物，涵盖2021年以来发表的文章。
