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3'-Methyl-4-thio-1H-tetrahydropyranspiro-5'-hydantoin Platinum Complex As a Novel Potent Anticancer Agent and Xanthine Oxidase Inhibitor

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Specialty Pharmacy
Date 2020 Apr 25
PMID 32329137
Citations 3
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Abstract

In this study, a Pt(IV) complex with 3'-methyl-4-thio-1H-tetrahydropyranspiro-5'-hydantoin (complex 1) was synthesized. The structure was determined via elemental analyses, infrared, H, and C nuclear magnetic resonance techniques. Density functional theory calculations were applied to optimize the molecular geometry and to calculate structural parameters and vibrational frequencies. The cytotoxicity of the newly synthesized complex 1 was assessed against K-562 and REH cells and compared with the cytotoxic effects of the ligand (L) and its Pd(IV) complex (complex 2). Complex 1 exhibited a better cytotoxic activity (IC  = 76.9 µM against K-562 and 15.6 µM against REH cells) than L and complex 2, which was closer to the cytotoxic effect of cisplatin (IC  = 36.9 μM and 1.07 μM against K-562 and REH cells, respectively), as compared with the ligand and complex 2. L and its complexes 1 and 2 were evaluated for inhibitory activity against xanthine oxidase (XO) in vitro, as compared with allopurinol (IC  = 1.70 μM). Complex 1 was shown as a potent XO inhibitor, with an IC value of 19.33 μM, and the binding mode with the enzyme was predicted by molecular docking. Its inhibitory activity against XO is a potential advantage that might result in improved profile and anticancer activity.

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