DFT-based reactivity and combined QSAR, molecular docking of 1,2,4,5-Tetrazine derivatives as inhibitors of Pim-1 kinase

Heliyon

Toufik Salah¹  Halima Hazhazi¹  Nadjib Melkemi¹  Mohammed Bouachrine² 

[1] Group of Computational and Pharmaceutical Chemistry, Laboratory of Molecular Chemistry and Environment (LMCE), Department of Chemistry of Sciences, University of Biskra, 07000, Biskra, Algeria;MCNS Laboratory, Faculty of Science, Moulay Ismail University of Meknes, Morocco;

关键词: Pharmaceutical chemistry;    Theoretical chemistry;    Bioinformatics;    1,2,4,5-Tetrazines;    Antitumor activity;    DFT;   

DOI  :  

来源: DOAJ

【 摘 要 】

In the present work we have calculated several DFT reactivity descriptors for 1,2,4,5-Tetrazine at the B3LYP/6–311++G(d,p) level of theory in order to analyze its reactivity in vacuum and solvent phases. Whereas, the influence of the solvent was taken into account employing the PCM model. DFT-based descriptors such as (electronic chemical potential, electrophilicity, condensed Fukui function….) have been determined to predict the reactivity of 1,2,4,5-Tetrazine. A series of eighteen 1,2,4,5-Tetrazine derivatives was studied by using two computational techniques, namely, quantitative structure activity relationship (QSAR) and molecular docking. QSAR models of the antitumor activity of some 1,2,4,5-Tetrazine derivatives were established in gas and solvent phases which exhibited good statistical values for both cases. Whereas, multiple linear regression (MLR) procedure was used to obtain the best QSAR models and the leave-one-out (LOO) method to estimate the predictivity of our models. The most and the least active compounds were docked with the protein (3C4E) to confirm those obtained results from QSAR models and elucidate the binding mode between this type of compounds and corresponding protein.

【 授权许可】

Unknown