Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), University of Porto, Edifício do Terminal de Cruzeiros do Porto de Leixões, Avenida General Norton de Matos S/N, 4450-208 Matosinhos, Portugal.
Int J Mol Sci. 2024 Jan 30;25(3):1691. doi: 10.3390/ijms25031691.
Recently, the diarylpentanoid () has been identified as a potent in vitro growth inhibitor of cancer cells, with a GI value between 0.17 and 0.45 µM, showing low toxicity in non-tumor cells. () promotes mitotic arrest by interfering with mitotic spindle assembly, leading to apoptotic cell death. Following on from our previous work, we designed and synthesized a library of () analogs and evaluated the cell growth inhibitory activity of three human cancer cell lines within this library in order to perform structure-activity relationship (SAR) studies and to obtain compounds with improved antimitotic effects. Four compounds (, , , and ) were active, and the growth inhibition effects of compounds , , and were associated with a pronounced arrest in mitosis. These compounds exhibited a similar or even higher mitotic index than (), with compound displaying the highest antimitotic activity, associated with the interference with mitotic spindle dynamics, inducing spindle collapse and, consequently, prolonged mitotic arrest, culminating in massive cancer cell death by apoptosis.
最近， diarylpentanoid () 被鉴定为一种有效的体外癌细胞生长抑制剂，其 GI 值在 0.17 到 0.45 µM 之间，对非肿瘤细胞的毒性较低。() 通过干扰有丝分裂纺锤体的组装来促进有丝分裂停滞，导致细胞凋亡。基于我们之前的工作，我们设计并合成了 () 类似物文库，并在该文库中评估了三种人癌细胞系的细胞生长抑制活性，以便进行构效关系 (SAR) 研究，并获得具有改善抗有丝分裂作用的化合物。四种化合物 (、、、和) 具有活性，化合物 、 、和 的生长抑制作用与有丝分裂的明显停滞有关。这些化合物表现出与 () 相似甚至更高的有丝分裂指数，其中化合物 显示出最高的抗有丝分裂活性，与干扰有丝分裂纺锤体动力学有关，导致纺锤体崩溃，从而导致有丝分裂停滞延长，最终通过细胞凋亡导致大量癌细胞死亡。
