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

Autor: Khoury A; School of Science, Western Sydney University, Locked Bag 1797, Penrith South, NSW 2751, Australia., Elias E; School of Natural Sciences, School of Arts and Sciences, Lebanese American University, P.O. Box 36, Byblos Lebanon., Mehanna S; School of Natural Sciences, School of Arts and Sciences, Lebanese American University, P.O. Box 36, Byblos Lebanon., Shebaby W; School of Natural Sciences, School of Arts and Sciences, Lebanese American University, P.O. Box 36, Byblos Lebanon., Deo KM; School of Science, Western Sydney University, Locked Bag 1797, Penrith South, NSW 2751, Australia., Mansour N; School of Natural Sciences, School of Arts and Sciences, Lebanese American University, P.O. Box 36, Byblos Lebanon., Khalil C; School of Natural Sciences, School of Arts and Sciences, Lebanese American University, P.O. Box 36, Byblos Lebanon., Sayyed K; School of Natural Sciences, School of Arts and Sciences, Lebanese American University, P.O. Box 36, Byblos Lebanon., Sakoff JA; Calvary Mater Newcastle Hospital, Waratah, NSW 2298, Australia., Gilbert J; Calvary Mater Newcastle Hospital, Waratah, NSW 2298, Australia., Daher CF; School of Natural Sciences, School of Arts and Sciences, Lebanese American University, P.O. Box 36, Byblos Lebanon., Gordon CP; School of Science, Western Sydney University, Locked Bag 1797, Penrith South, NSW 2751, Australia., Taleb RI; School of Natural Sciences, School of Arts and Sciences, Lebanese American University, P.O. Box 36, Byblos Lebanon., Aldrich-Wright JR; School of Science, Western Sydney University, Locked Bag 1797, Penrith South, NSW 2751, Australia.
Jazyk: angličtina
Zdroj: Journal of medicinal chemistry [J Med Chem] 2022 Dec 22; Vol. 65 (24), pp. 16481-16493. Date of Electronic Publication: 2022 Dec 08.
DOI: 10.1021/acs.jmedchem.2c01310
Abstrakt: 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.
Databáze: MEDLINE
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