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Docking Approach to Predict Inhibition Activity of New Pt(II) Complexes Against Kinase Protein and Human DNA: Full Characterization, HF-FC Modeling and Genotoxicity

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Abstract

New series of Pt(II)–azaindazole complexes, were synthesized and also characterized by, analytical, spectral and computational tools. All synthesized Pt(II)-complexes, appeared as mononuclear with bi-dentate mode of bonding. Octahedral arrangement as well as square-planer, were proposed geometries around platinum atoms in all complexes. The best atomic-skeletons, were demonstrated by using Gaussian09 program. Applying MOE module (V. 2015), extensive molecular docking process was executed upon all new synthesizes. This docking study was interested in kinase protein (3ce3) and health cell–DNA (5ahr), to predict the degree of cancer-inhibition and also the mode of interaction. A significant inhibition activity, was clearly predicted with Pt(II)–4b and Pt(II)–4c complexes, against 3ce3 protein-receptors. While the absence of any significant effect towards 5ahr, which is favorable trend of therapeutic agent. Various backbone receptors (amino acids) were attacked through H-bonding, from most tested inhibitors, especially of 3ce3 protein. DNA-degradation study, which executed in vitro, displayed a complete degradation for DNA with most screened compounds except 4d and 4e derivatives. This feature points to the promising antitumor activity of most synthesizes, especially the Pt(II) complexes, as a predicted role of its complexes.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, Mecca, Saudi Arabia

    Nashwa El-Metwaly, Jabir H. Al-Fahemi, Ismail Althagafi, Abdalla M. Khedr & Hanadi A. Katouah

  2. Department of Chemistry, Faculty of Science, Mansoura University, Mansoura, Egypt

    Nashwa El-Metwaly

  3. Department of Chemistry, Faculty of Science, Tanta University, Tanta, Egypt

    Abdalla M. Khedr

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  1. Nashwa El-Metwaly
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El-Metwaly, N., Al-Fahemi, J.H., Althagafi, I. et al. Docking Approach to Predict Inhibition Activity of New Pt(II) Complexes Against Kinase Protein and Human DNA: Full Characterization, HF-FC Modeling and Genotoxicity. J Inorg Organomet Polym 30, 907–922 (2020). https://doi.org/10.1007/s10904-019-01233-w

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