Methyl thiophanate as a DNA minor groove binder produces MT–Cu(II)–DNA ternary complex preferably with AT rich region for initiation of DNA damage

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• 作者：Quaiser Saquib ; Abdulaziz A. Al-Khedhairy ; Saud A. Alarifi ; Sansa Dutta ; Swagata Dasgupta ; Javed Musarrat
• 关键词：Fungicide ; Fluorescence quenching ; Methyl thiophanate ; Circular dichroism ; Cyclic voltammetry ; DNA binding
• 刊名：International Journal of Biological Macromolecules
• 出版年：2010
• 出版时间：1 July 2010
• 年：2010
• 卷：47
• 期：1
• 页码：68-75
• 全文大小：901 K

文摘

Interaction of a genotoxic fungicide methyl thiophanate (MT) has been studied in vitro with calf thymus DNA. Fluorescence quenching data revealed the binding constant (K_a = 3.23 × 10⁴ M⁻¹) and binding capacity (n = 1.1) of MT with ctDNA. Ligand displacement studies using specific probes suggested the MT binding at DNA minor groove. The docking analysis further substantiated MT interaction with at least three AT base pairs within the DNA groove. A discernable change in E₀′ value with decreased peak currents in cyclic voltammogram, and peak shifts in CD spectra reflected the formation of MT–ctDNA and MT–ctDNA–Cu(II) complexes. The results elucidate the significance of specific MT–DNA interactions as an initiating event in MT-induced DNA damage.