In silico design of novel Pyrazole derivatives containing thiourea skeleton as anti-cancer agents using: 3D QSAR, Drug-Likeness studies, ADMET prediction and molecular docking

Mchichi, L. El; Aissouq, Abdellah El; Kasmi, Rania; Belhassan, Assia; El-Mernissi, Reda; Ouammou, Abdelkrim; Lakhlifi, Tahar; Bouachrine, Mohammed

doi:10.1016/j.matpr.2021.03.152

Cited by 26 publications

(9 citation statements)

References 39 publications

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“…The robustness of the developed model was evaluated through internal and external validations. 13,14 The internal validation was performed using the leave-one-out cross-validation method. In this process, each compound in the training set was eliminated, and the remaining dataset ( n − 1) was used to develop a model and predict the target value of the compound that has been removed.…”

Section: Methodsmentioning

confidence: 99%

Computer-aided drug design applied to a series of pyridinyl imidazole derivatives targeting p38α MAP kinase: 2D-QSAR, docking, MD simulation, and ADMET investigations

et al. 2022

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Section: Methodsmentioning

confidence: 99%

Computer-aided drug design applied to a series of pyridinyl imidazole derivatives targeting p38α MAP kinase: 2D-QSAR, docking, MD simulation, and ADMET investigations

et al. 2022

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“…The database structures were designed and optimized and again saved in mol2 format utilizing SYBYL X2.0 software [21]. Biological activity data of nitroisoxazole derivatives in these literatures are expressed as Ki (10-6 M), and we have converted them to logarithmic pki (-Log ki).…”

Section: Data Set Sourcementioning

confidence: 99%

Computational investigation of pyrrolidin derivatives as novel GPX4/MDM2–p53 inhibitors using 2D/3D-QSAR, Molecular docking, Molecular dynamics simulations and MM-GBSA free energy

Tabti

Sbai

Elmchichi

et al. 2022

Preprint

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The p53 is a tumor suppressor protein that adjusts cell cycle and growth arrest as well as genes that restore DNA damage and apoptosis. Murine double minute 2 (MDM2) is a main p53 antagonist. We created a novel QSAR model using a series of highly active spiro [pyrrolidin-3,2-oxindoles] that consisted of 29 compounds that were experimentally validated to inhibit the MDM2-p53 interaction. Three optimal models have been developed CoMFA/E+S, CoMSIA/S+H+A and HQSAR have revealed good statistical results, but the CoMSIA mode only which validates all the external validation tests applied successfully. Based on the CoMSIA/S+H+A model was carefully chosen to design four compounds with values of inhibitory activity greater than the highly active compound in the data set. The Newly designed compounds were docked in the target receptor binding site (ID: 4LWU). The newly designed compound Pred 01 showed the highest affinity with a value of -9.4kcal / mol, while compound N°04 which represents the data set and control compound (Nutlin-3) showed binding energies of the order of -8.8 kcal / mol and -8.2kcal / mol, respectively. In addition, the roles of lipinski and veber were estimated, the results obtained demonstrate that the proposed molecules involve good oral bioavailability and an ability to diffuse through different biological barriers. For in-depth study, The Pred01 / receptor, N°04 / receptor and Nutlin-3 / receptor complexes were selected via dynamic simulation analyzes with a simulation time of 100 ns and, also their free binding energy was examined operating the MM-GBSA approach. The molecular docking results obtained accentuate the crucial residues responsible for the ligand / protein interaction, providing insight into the mode of interaction. The MD simulation analysis confirms the conformational stability of the selected complexes during the MD trajectory, and the fluctuations recorded are insignificant. The results of MM-GBSA reveal that the new compound Pred 01 exhibits the lowest free energy, which confirms the result of molecular docking.

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“…Molecular docking is one of the most virtual screening methods, especially when the 3D structure of the receptor is available [57][58][59]. Here, the X-ray diffraction structure of monoamine oxidase B (MAO-B) was downloaded from the protein database bank (PDB ID: 2BK3) [60].…”

Section: Docking Studymentioning

confidence: 99%

Computational investigation of unsaturated ketone derivatives as MAO-B inhibitors by using QSAR, ADME/Tox, molecular docking and molecular dynamics simulations

2021

Turk J Chem

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Computer-aided drug design (CADD) approaches have recently become essential in drug discovery. These techniques proved to be effective in various stages of the drug development process, reducing both the cost and time required to develop a drug compared to conventional methods [21]. In general, CADD approaches are classified into two types: structure-based drug design (SBDD) and ligand-based drug design (LBDD). When the 3D structure of the protein is

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In silico design of novel Pyrazole derivatives containing thiourea skeleton as anti-cancer agents using: 3D QSAR, Drug-Likeness studies, ADMET prediction and molecular docking

Cited by 26 publications

References 39 publications

Computer-aided drug design applied to a series of pyridinyl imidazole derivatives targeting p38α MAP kinase: 2D-QSAR, docking, MD simulation, and ADMET investigations

Computer-aided drug design applied to a series of pyridinyl imidazole derivatives targeting p38α MAP kinase: 2D-QSAR, docking, MD simulation, and ADMET investigations

Computational investigation of pyrrolidin derivatives as novel GPX4/MDM2–p53 inhibitors using 2D/3D-QSAR, Molecular docking, Molecular dynamics simulations and MM-GBSA free energy

Computational investigation of unsaturated ketone derivatives as MAO-B inhibitors by using QSAR, ADME/Tox, molecular docking and molecular dynamics simulations

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