Structural investigation of tetrahydropteridin analogues as selective PLK1 inhibitors for treating cancer through combined QSAR techniques, molecular docking, and molecular dynamics simulations

Tong, Jianbo; Luo, Ding; Bian, Shuai; Zhang, Xing

doi:10.1016/j.molliq.2021.116235

Cited by 19 publications

(5 citation statements)

References 66 publications

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“…The predicted ADMET properties of anonaine with different parameters analyzed by the PreADMET tool shown in Supplementary Table 2, suggest that anonaine has moderate toxicity and no carcinogenic potential. All values obtained in the results with anonaine were compared to standard values reported in the literature (Ames et al, 1972;Yee, 1997;Van De Waterbeemd and Gifford, 2003;Alliance, 2016;Wadapurkar et al, 2018;Ferreira et al, 2020;Pereira, 2021;Tong et al, 2021). Also, it is suggested that natural alkaloid anonaine is less toxic to mammals than cypermethrin.…”

Section: Discussionmentioning

confidence: 84%

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Anonaine from Annona crassiflora inhibits glutathione S-transferase and improves cypermethrin activity on Rhipicephalus (Boophilus) microplus (Canestrini, 1887)

Bezerra¹,

Tavares²,

Rocha³

et al. 2022

Experimental Parasitology

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Section: Discussionmentioning

confidence: 84%

“…ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties of anonaine were analyzed using PreADMET software (Kwang, 2005). The ADMET analyses were carried out according to the specific classifications and parameters (Van De Waterbeemd and Gifford, 2003;Tong et al, 2021).…”

Section: Anonaine Structure and Admet Featuresmentioning

confidence: 99%

Anonaine from Annona crassiflora inhibits glutathione S-transferase and improves cypermethrin activity on Rhipicephalus (Boophilus) microplus (Canestrini, 1887)

Bezerra¹,

Tavares²,

Rocha³

et al. 2022

Experimental Parasitology

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“…Then, an energy gradient convergence criterion of 0.005 kcal (mol Å) À 1 with a maximum number of 10000 iterations was applied to minimise the energy of each compound utilising the Gasteiger-Hückel charges and the standard Tripos force field from the Powell method. [20,21] Other parameters kept the default values in SYBYL-X 2.0.…”

Section: Data Sources and Structure Preparationmentioning

confidence: 99%

Drug Design, Molecular Docking and Molecular Dynamics Simulations of Indole Class HIV‐1 NNRTIs Explored with QSAR and Topomer Search

et al. 2023

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HIV reverse transcriptase (RT) as one of the key targets for the treatment of HIV, and in recent years a series of indole class non‐nucleoside reverse transcriptase inhibitors (NNRTIs) with potent anti‐HIV‐1 properties have been reported. In this paper, Topomer CoMFA model with reliable validation results (q2=0.809, R2=0.983, R2pred=0.870) for exploring the quantitative structure‐activity relationship (QSAR) of the inhibitors. And the relationship between molecular structures and activities were further analysed using the contour plots. The Topomer search technique was employed to search and then designed novel compounds with stronger inhibitory effects. Molecular docking showed that the residue LYS101, GLU138 and ILE180 played a key role, meanwhile, the stability of the docking results was verified by molecular dynamics simulations (MD). Finally, the calculated results of the binding free energy calculations agree with the predictions of the model, further validating the reliability of the proposed model.

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“…The standard Tripos molecular force field and Powell energy gradient algo-rithm are used for energy optimization. All molecules are loaded with Gasteger-Huckel charges, the maximum number of iterations is 1000, the energy convergence limit is set to 0.005 kcal • mol-1, and the other parameters adopt the system default values [14,15].…”

Section: Datasetmentioning

confidence: 99%

QSAR study, molecular docking and molecular dynamic simulation of Aurora kinase inhibitors derived from imidazo[4,5-b]pyridine derivatives

Tong

Xiao

Bian

et al. 2022

Preprint

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Cancer is a serious threat to human life and social development and the use of scientific methods for cancer prevention and control is necessary. In this study, HQSAR, CoMFA, CoMSIA and TopomerCoMFA methods were used to establish models of 65 imidazo[4,5-b]pyridine derivatives to explore the quantitative structure activity relationship between their anticancer activities and molecular conformations. The results showed that the cross-validation coefficients q2 of HQSAR, CoMFA, CoMSIA and TopomerCoMFA were 0.892, 0.866, 0.877 and 0.905, respectively. The non-cross-validation coefficients r2 were 0.948, 0.983, 0.995 and 0.971, respectively. The externally validated complex correlation coefficients r2pred of external validation were 0.814, 0.829, 0.758 and 0.855, respectively. The PLS analysis verified the QSAR models we established with high prediction ability and stability. Based on these statisticians, virtual screening based on R group was done in ZINC database by using the Topomer search technology. Finally, 10 new compounds with higher activity were designed with the screened new fragments. In order to explore the binding modes and targets between ligands and protein receptors, these newly designed compounds were conjugated with macromolecular protein (PDB ID: 1MQ4) by molecular docking technology. Furthermore, to study the nature of newly designed compound in dynamic states and the stability of protein-ligand complex, molecular dynamics simulation for 50ns was carried out for N3, N4, N5 and N7 docked with 1MQ4 protease structure. Free energy landscape was computed to search the most stable conformation. These results proved the efficient and stability of the newly designed compounds. Finally, ADMET was used to predict the pharmacology and toxicity of the designed 10 drug molecules to test their pharmacological effects and safety.

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Structural investigation of tetrahydropteridin analogues as selective PLK1 inhibitors for treating cancer through combined QSAR techniques, molecular docking, and molecular dynamics simulations

Cited by 19 publications

References 66 publications

Anonaine from Annona crassiflora inhibits glutathione S-transferase and improves cypermethrin activity on Rhipicephalus (Boophilus) microplus (Canestrini, 1887)

Anonaine from Annona crassiflora inhibits glutathione S-transferase and improves cypermethrin activity on Rhipicephalus (Boophilus) microplus (Canestrini, 1887)

Drug Design, Molecular Docking and Molecular Dynamics Simulations of Indole Class HIV‐1 NNRTIs Explored with QSAR and Topomer Search

QSAR study, molecular docking and molecular dynamic simulation of Aurora kinase inhibitors derived from imidazo[4,5-b]pyridine derivatives

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