Design and development of novel spiro-oxindoles as potent antiproliferative agents using quantitative structure activity based Monte Carlo method, docking molecular, molecular dynamics, free energy calculations, and pharmacokinetics /toxicity studies

Tabti, Kamal; Abdessadak, Oumayma; Sbai, Abdelouahid; Maghat, Hamid; Bouachrine, Mohammed; Lakhlifi, Tahar

doi:10.1016/j.molstruc.2023.135404

Cited by 19 publications

(4 citation statements)

References 52 publications

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“…The main advantage of the Monte Carlo method is the use of randomness to solve problems that, in principle, may be more or less deterministic. Nowadays, computers easily supply randomness to the interested user through random variable generators [50][51][52][53][54][55][56][57][58][59][60]. The models considered are certainly largely random.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Structure–Activity Relationship Models for the Angiotensin-Converting Enzyme Inhibitory Activities of Short-Chain Peptides of Goat Milk Using Quasi-SMILES

Toropova,

Toropov,

Roncaglioni

et al. 2024

Macromol

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The inhibitory activity of peptides on angiotensin-converting enzyme (ACE) is a measure of their antihypertensive potential. Quantitative structure–activity relationship (QSAR) models obtained based on the analysis of sequences of amino acids are suggested. The average determination coefficient for the active training sets is 0.36 ± 0.07. The average determination coefficient for validation sets is 0.79 ± 0.02. The paradoxical situation is caused by applying the vector of ideality of correlation, which improves the statistical quality of a model for the calibration and validation sets but is detrimental to the statistical quality of models for the training sets.

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Section: Discussionmentioning

confidence: 99%

Quantitative Structure–Activity Relationship Models for the Angiotensin-Converting Enzyme Inhibitory Activities of Short-Chain Peptides of Goat Milk Using Quasi-SMILES

Toropova,

Toropov,

Roncaglioni

et al. 2024

Macromol

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“…Using the structural information generated by the QSAR models, we designed five new inhibitors that were more potent than the original compounds [24] . To strengthen the results of our models, we also conducted binding free energy calculations, molecular docking, and ADME/Tox studies [25,26] . The ultimate objective of this study is to establish a theoretical foundation for identifying new colchicine binding site inhibitors based on 4‐arylpiperazine‐1‐carbonyl‐2H‐1,2,3‐triazole.…”

Section: Introductionmentioning

confidence: 99%

“…[24] To strengthen the results of our models, we also conducted binding free energy calculations, molecular docking, and ADME/Tox studies. [25,26] The ultimate objective of this study is to establish a theoretical foundation for identifying new colchicine binding site inhibitors based on 4-arylpiperazine-1-carbonyl-2H-1,2,3-triazole.…”

Section: Introductionmentioning

confidence: 99%

Computational Exploration of the Structural Requirements of Triazole Derivatives as Colchicine Binding Site Inhibitors

et al. 2023

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Colchicine inhibits microtubule assembly by preventing tubulin polymerization, making the colchicine binding site a promising target against cancer. The present study focuses on the 3D‐QSAR analysis of 31 triazole analogs. The atom‐based and field‐based QSAR models exhibit significant statistical results for internal and external validations, with the atom‐based 3D‐QSAR model showing a Q2 of 0.658 and R2 of 0.998, and the field‐based 3D‐QSAR model showing a Q2 of 0.658 and R2 of 0.998. The 3D‐QSAR atom‐based pharmacophore model explains biological activity using a six‐point hypothesis (AHHRRR.1), while the field‐based 3D‐QSAR model explains activity based on steric, electrostatic, hydrophobic, and hydrogen bond donor/acceptor fields. Based on the 3D contour maps generated, five new compounds were designed and their ADME/Tox properties predicted. The results suggested that these compounds possess potent pharmacological characteristics. The results of the molecular docking analysis showed that Pred01 and Pred02 had higher docking scores (−6.2417Kcal/mol and −6.5049Kcal/mol, respectively) than compound 15, and they formed notable hydrogen bonds and hydrophobic interactions with active site residues. The MMGBSA results confirmed these findings and emphasized the essential role of van der Waals energy in the binding energy. Moreover, the dynamic stability of the complexes was further supported by MD simulations.

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“…22 Molecular docking and molecular dynamics simulations are also highly useful techniques that provide accurate data on the interaction between ligands and proteins in the physiological environment. 23,24 Together, these methods have revolutionized drug discovery and continue to be instrumental in developing new treatments. Hence, we can better understand ligand–receptor interactions using integrated computational methods, ultimately creating more potent small molecules.…”

Section: Introductionmentioning

confidence: 99%

Computational investigation of novel pyrimidine derivatives as potent FAK inhibitorsvia3D-QSAR, molecular docking, molecular dynamics simulation and retrosynthesis

El Bahi,

Boutalaka,

El Alaouy

et al. 2023

New J. Chem.

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Design and development of novel spiro-oxindoles as potent antiproliferative agents using quantitative structure activity based Monte Carlo method, docking molecular, molecular dynamics, free energy calculations, and pharmacokinetics /toxicity studies

Cited by 19 publications

References 52 publications

Quantitative Structure–Activity Relationship Models for the Angiotensin-Converting Enzyme Inhibitory Activities of Short-Chain Peptides of Goat Milk Using Quasi-SMILES

Quantitative Structure–Activity Relationship Models for the Angiotensin-Converting Enzyme Inhibitory Activities of Short-Chain Peptides of Goat Milk Using Quasi-SMILES

Computational Exploration of the Structural Requirements of Triazole Derivatives as Colchicine Binding Site Inhibitors

Computational investigation of novel pyrimidine derivatives as potent FAK inhibitorsvia3D-QSAR, molecular docking, molecular dynamics simulation and retrosynthesis

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