Khoury Aleen, Elias Elias, Mehanna Stephanie, Shebaby Wassim, Deo Krishant M, Mansour Najwa, Khalil Christian, Sayyed Katia, Sakoff Jennette A, Gilbert Jayne, Daher Costantine F, Gordon Christopher P, Taleb Robin I, Aldrich-Wright Janice R
School of Science, Western Sydney University, Locked Bag 1797, Penrith South, NSW 2751, Australia.
School of Natural Sciences, School of Arts and Sciences, Lebanese American University, P.O. Box 36, Byblos Lebanon.
J Med Chem. 2022 Dec 22;65(24):16481-16493. doi: 10.1021/acs.jmedchem.2c01310. Epub 2022 Dec 8.
A novel platinum(II) complex and its platinum(IV) derivative were synthesized and characterized. Cytotoxicity studies against mesenchymal cells (MCs) and lung (A549), breast (MDA-MB-231), and melanoma (A375) cancer cells demonstrated 7-20-fold superior activity for both complexes relative to cisplatin. Remarkably, demonstrated 17-22-fold greater selectivity toward the cancerous cells compared to the non-cancerous MCs. Western blot analysis on A549 cells showed the involvement of the intrinsic apoptotic pathway. Cellular fractionation and uptake experiments in A549 cells using ICP-mass spectrometry (MS) indicated that and cross the cellular membrane predominantly via active transport mechanisms. The significant improvement in selectivity that is exhibited by is reported for the first time for this class of complexes.
合成并表征了一种新型铂（II）配合物及其铂（IV）衍生物。针对间充质细胞（MCs）以及肺癌（A549）、乳腺癌（MDA-MB-231）和黑色素瘤（A375）癌细胞的细胞毒性研究表明，这两种配合物的活性比顺铂高7至20倍。值得注意的是，与非癌细胞MCs相比，其对癌细胞的选择性高17至22倍。对A549细胞的蛋白质免疫印迹分析表明内源性凋亡途径参与其中。使用电感耦合等离子体质谱（ICP-MS）对A549细胞进行的细胞分级分离和摄取实验表明，该配合物主要通过主动转运机制穿过细胞膜。此类配合物首次报道了其在选择性方面的显著改善。
