Drug repurposing plays a vital role in the discovery of undescribed bioactivities in clinical drugs. Based on drug repurposing strategy, we for the first time reported a novel series of troxipide analogs and then evaluated their antiproliferative activity against MCF-7, PC3, MGC-803, and PC9 cancer cell lines and WPMY-1, most of which showed obvious selectivity toward PC-3 over the other three cancer cell lines and WPMY-1. Compound 5q, especially, could effectively inhibit PC3 with an IC₅₀ value of 0.91 μM, which exhibited around 53-fold selectivity toward WPMY-1. Data indicated that 5q effectively inhibited the colony formation, suppressed the cell migration, and induced G1/S phase arrest in PC3 cells. Also, compound 5q induced cell apoptosis by activating the two apoptotic signaling pathways in PC3 cells: death receptor-mediated extrinsic pathway and mitochondria-mediated intrinsic pathway. Compound 5q up-regulated the expression of both pro-apoptotic Bax and P53, while down-regulated anti-apoptotic Bcl-2 expression. Besides, compound 5q significantly increased the expression of cleaved caspase 3/9 and cleaved PARP. Therefore, the successful discovery of compound 5q may further validate the feasibility of this theory, which will encourage researchers to reveal undescribed bioactivities in traditional drugs.

改变用途的药物在发现临床药物中未描述的生物活性中起着至关重要的作用。基于药物重用策略，我们首次报道了一系列新的troxipide类似物，然后评估了它们对MCF-7，PC3，MGC-803和PC9癌细胞系和WPMY-1的抗增殖活性，其中大多数表现出明显的对PC-3的选择性优于其他三种癌细胞系和WPMY-1。尤其是化合物5q，可以有效抑制PC3，IC ₅₀值为0.91μM，对WPMY-1的选择性约为53倍。数据表明5q有效抑制了PC3细胞中的集落形成，抑制了细胞迁移并诱导了G1 / S期阻滞。另外，化合物5q通过激活PC3细胞中的两个凋亡信号传导途径诱导细胞凋亡：死亡受体介导的外在途径和线粒体介导的内在途径。化合物5q上调凋亡前Bax和P53的表达，同时下调抗凋亡Bcl-2的表达。此外，化合物5q显着增加了裂解的半胱天冬酶3/9和裂解的PARP的表达。因此，化合物5q的成功发现可能进一步证实该理论的可行性，这将鼓励研究人员揭示传统药物中未描述的生物活性。