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Novel Platinum(II) and Platinum(IV) Antitumor Agents that Exhibit Potent Cytotoxicity and Selectivity.

Aleen KhouryElias EliasStephanie MehannaWassim ShebabyKrishant M DeoNajwa MansourChristian KhalilKatia SayyedJennette A SakoffJayne GilbertCostantine F DaherChristopher P GordonRobin I TalebJanice Rae Aldrich-Wright
Published in: Journal of medicinal chemistry (2022)
A novel platinum(II) complex 47OMESS(II) and its platinum(IV) derivative 47OMESS(IV) 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, 47OMESS(IV) 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 47OMESS(II) and 47OMESS(IV) cross the cellular membrane predominantly via active transport mechanisms. The significant improvement in selectivity that is exhibited by 47OMESS(IV) is reported for the first time for this class of complexes.
Keyphrases
  • induced apoptosis
  • cell cycle arrest
  • mass spectrometry
  • cell death
  • endoplasmic reticulum stress
  • multiple sclerosis
  • stem cells
  • oxidative stress
  • signaling pathway
  • anti inflammatory
  • cell proliferation