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3′‐Methyl‐4‐thio‐1 H ‐tetrahydropyranspiro‐5′‐hydantoin platinum complex as a novel potent anticancer agent and xanthine oxidase inhibitor
Author(s) -
Cherneva Emiliya,
Atanasova Mariyana,
Buyukliev Rossen,
Tomovic Katarina,
Smelcerovic Zaklina,
Bakalova Adriana,
Smelcerovic Andrija
Publication year - 2020
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.202000039
Subject(s) - chemistry , xanthine oxidase , stereochemistry , hydantoin , thio , cytotoxicity , ligand (biochemistry) , docking (animal) , cisplatin , molecular model , enzyme , in vitro , biochemistry , receptor , medicine , nursing , surgery , chemotherapy
In this study, a Pt(IV) complex with 3 ′ ‐methyl‐4‐thio‐1 H ‐tetrahydropyranspiro‐5′‐hydantoin (complex 1 ) was synthesized. The structure was determined via elemental analyses, infrared, 1 H, and 13 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 50  = 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 50  = 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 50  = 1.70 μM). Complex 1 was shown as a potent XO inhibitor, with an IC 50 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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