化学
顺铂
前药
细胞毒性
萘普生
药理学
癌细胞
体外
奥沙利铂
药品
立体化学
生物化学
癌症
化疗
结直肠癌
病理
外科
替代医学
内科学
医学
作者
Xiao Liu,Dominik Wenisch,Philipp Dahlke,Paul M. Jordan,Michael A. Jakupec,Christian R. Kowol,Phil Liebing,Oliver Werz,Bernhard K. Keppler,Wolfgang Weigand
标识
DOI:10.1016/j.ejmech.2023.115515
摘要
In the last decades, inflammation has been recognized as being closely connected to cancer, and joint strategies encompassing chemotherapeutic and anti-inflammatory agents have been extensively studied. In this work, a series of novel cisplatin and oxaliplatin-based Pt(IV) complexes comprising non-steroidal anti-inflammatory drugs (NSAIDs) and their carboxyl ester analogues as axial moieties were synthesized. Several of the cisplatin-based Pt(IV) complexes 22–30 showed increased cytotoxicity in the human cancer cell lines CH1/PA-1, SW480 and A549 compared to the Pt(II) drug. For the most potent complex 26, comprising two aceclofenac (AFC) moieties, the formation of Pt(II)-9-methylguanine (9-MeG) adducts after activation with ascorbic acid (AsA) was proven. Additionally, a significant inhibition of cyclooxygenase (COX) activity and prostaglandin E2 (PGE2) production was observed, as well as increased cellular accumulation, depolarization of mitochondrial membranes, and strong proapoptotic potencies in SW480 cells. Overall, these systematic effects shown in vitro confer 26 as a potential anticancer agent combined with anti-inflammatory properties.
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