Biocompatibility and bioactivity study of a cytostatic drug belonging to the group of alkylating agents of the triazine derivative class

•Bioactivity and biocompatibility of a cytostatic drug belonging to a triazine derivative class were investigated.•The calculated value of a binding constant (Ka = 3.44⋅107 M−1) indicates the formation of covalent adducts with DNA.•High haemocompatibility and dose-dependent cytostatic activity towar...

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Veröffentlicht in:Journal of molecular liquids 2021-12, Vol.343, p.117630, Article 117630
Hauptverfasser: Mikolaichuk, Olga V., Sharoyko, Vladimir V., Popova, Elena A., Protas, Alexandra V., Fonin, Alexander V., Vasina, Lubov V., Anufrikov, Yurii A., Luttsev, Mikhail D., Nashchekina, Iuliia A., Malkova, Anna M., Tochilnikov, Grigorii V., Ageev, Sergei V., Semenov, Konstantin N.
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Sprache:eng
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Zusammenfassung:•Bioactivity and biocompatibility of a cytostatic drug belonging to a triazine derivative class were investigated.•The calculated value of a binding constant (Ka = 3.44⋅107 M−1) indicates the formation of covalent adducts with DNA.•High haemocompatibility and dose-dependent cytostatic activity towards tumour cell lines were observed. The article describes the study of biocompatibility and bioactivity of a cytostatic agent [5-[[4,6-bis(aziridin-1-yl)-1,3,5-triazin-2-yl]amino]-2,2-dimethyl-1,3-dioxan-5-yl]methanol (substance (a)). The compound was characterised by means of 1H and 13C NMR spectroscopy, IR spectroscopy, mass spectrometry. Biomedicinal investigations included haemocompatibility studies (spontaneous haemolysis, platelet aggregation, plasma-coagulation haemostasis, binding with human serum albumin and DNA); determination of antioxidant properties (reaction with 2,2-diphenyl-1-picrylhydrazyl, photo-induced haemolysis, photodynamic properties, NO-radical uptake); genotoxicity, as well as cytotoxicity using HEK-293, A549, PA-1, T98G, SK-HEP-1, PANC-1 cell lines. The article shows two possible mechanisms of the cytostatic action of the substance (a): due to its antioxidant activity and the possibility of the formation of adducts with DNA.
ISSN:0167-7322
1873-3166
DOI:10.1016/j.molliq.2021.117630