Molecular modelling of antiproliferative inhibitors based on SMILES descriptors using Monte-Carlo method, docking, MD simulations and ADME/Tox studies

Tabti, Kamal; Elmchichi, Larbi; Sbai, Abdelouahid; Maghat, Hamid; Bouachrine, Mohammed; Lakhlifi, Tahar

doi:10.1080/08927022.2022.2110246

Cited by 13 publications

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“…[13,14] This approach effectively identifies the relationship between molecular structure and bioactivity and key factors regulating compound activity. [15,16] Molecular docking and dynamics are powerful approaches for understanding the structural interactions between binding molecules and protein targets, predicting the optimal binding form. [17,18] Furthermore, absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) analysis can be used to evaluate the bioavailability and toxicity profile of molecules.…”

Section: Introductionmentioning

confidence: 99%

“…This approach effectively identifies the relationship between molecular structure and bioactivity and key factors regulating compound activity [15,16] . Molecular docking and dynamics are powerful approaches for understanding the structural interactions between binding molecules and protein targets, predicting the optimal binding form [17,18] .…”

Section: Introductionmentioning

confidence: 99%

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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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