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Nitrobenzene derivatives present an environmental concern to aquatic organisms, as well as a potential adverse effects on human health due to their toxicity. Therefore, monitoring nitrobenzene contamination levels is critical to protect both the ecosystem and the public. This study aims to quantitatively correlate the toxicity of nitrobenzene derivatives to their chemical structures using computational chemistry methods such as 3D‐QSPR, HQSPR, Molecular Docking and MD simulation. Additionally, to investigate the type of interactions and stability of nitrobenzene derivatives with the PP2 protein involved in the Phloem protein 2 (PP2). From each computational method a prediction model was extracted HQSPR (Atomic, Bonds, Donor/Acceptor, 3D‐QSPR (Steric, Electrostatic, Hydrophobic, Acceptor), and used for the design of X1 and X2 new nitrobenzene derivatives, which showed remarkable stability and better interactions. This study contributes to the understanding of the nitrobenzene derivatives' toxicity and offers materials towards the understanding of the mechanism of action of these substances in protein–ligand interactions. [ABSTRACT FROM AUTHOR]

Citrus essential oils (EOs) contain a variety of secondary metabolites, including coumarins (Cs), furocoumarins (FCs) and polymethoxyflavones (PMFs), all with different biological activities. While Regulation (EC) No 1334/2008 strictly regulates the use of coumarins, undesirable side effects of consuming furocoumarins remain without established maximum toxicity limits for human dietary intake. This study is based on an in‐silico approach aimed at determining these toxicity limits for the oxygenated heterocyclic compounds of citrus EOs approved for use in food. In addition, an innovative quantitative structure‐property relationship (QSPR) using the linear retention index system was explored to characterize the oxygenated heterocyclic compounds (COHs) present in these essential oils. Molecular docking of the studied compounds provided crucial insights into the structure‐odor relationships, offering insights into their mechanisms of action. In addition, an analysis of the pharmacokinetic and pharmacodynamic properties through ADME‐Tox deconstruction provides insight into the potential side effects of their consumption. The results are consolidated by dynamic simulations, providing crucial data for the development of regulations on the maximum toxicity limits of citrus EOs, given the health implications of the various compounds such as coumarins, furocoumarins and polymethoxyflavones present in these essential oils. [ABSTRACT FROM AUTHOR]

Microtubules are among the critical targets for chemotherapeutic agents to fight against cancer because of their crucial role in mitosis. Microtubule inhibitors block cell cycle progression and result in apoptosis, they can frequently disrupt microtubule/tubulin dynamics by binding to the α‐tubulin receptor. To this end, we have developed compounds against α‐tubulin receptor using several tools of computational chemistry: 3D‐QSAR, Molecular Docking, Molecular Dynamics Simulation, and ADMET prediction. The significant findings incorporated two reliable models: CoMFA (Q2=0.75; R2=0.89) and CoMSIA (Q2=0.57; R2=0.78). Molecular Docking was generated and validated using Molecular Dynamics simulation to investigate the binding mode between the most active compound and the α‐tubulin receptor. The results of the MD simulation demonstrated stability over a 100 ns period. Four compounds (C1, C2, C3, and C4) were developed based on the contour maps, and their activities were predicted. Additionally, Molecular Docking was executed to elucidate the interaction and affinity between the novel compounds and the α‐tubulin receptor. C1 exhibited high affinity and essential interactions and was subjected to MD simulation studies. The results of the MD simulation revealed that the modifications made to enhance the anticancer activity did not impact stability. Finally, ADMET analysis was utilized to examine drug‐likeness. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Investigation of new active therapeutic drugs against the emerging drug‐resistant Mycobacterium tuberculosis is a current medical and health challenge. Based on previously reported isoxazole‐based molecules that have a potent effect against Mycobacterium tuberculosis, computational methods were used in the current study to investigate the effect of isoxazole‐based molecules as a potential active drug‐resistant drug Mycobacterium tuberculosis H37Rv. Molecular models of isoxazole‐based molecules were established by 3D‐QSAR study, and different results were interpreted to propose 6 candidate agents more active than the previously reported compounds in the literature. Also, the candidate structures are more active than the therapeutic drug agent Isoniazid (NIH) against Mycobacterium Tuberculosis. Evaluation of the synthetic accessibility coefficient and the Lipinski properties of newly designed agent candidates indicate that these agents meet the criteria of a drug according to the Lipinski and Veber rules because they can be synthesized. In‐silico evaluation of ADMETox properties shows satisfactory results for most newly designed agent candidates. According to molecular docking, the drug candidates have a high score with a stable docked pose in the receptor (PDB code: 5v3y) compared to Isoniazid (NIH). The DFT and molecular dynamics study confirmed the previous results of 3D‐QSAR and molecular docking models. [ABSTRACT FROM AUTHOR]

Peroxiredoxin 5 (1HD2) is an antioxidant enzyme that catalyzes the decrease of peroxide, and act as a regulator of Redox signaling. It is a potential target for working on new antioxidants. 3D‐QSAR method was applied to a set of isoxazoles by using the comparative analysis of molecular fields (CoMFA and CoMSIA). Five new drug candidates (Pr1–Pr5) have been proposed. The study of the interactions between the drug candidate and antioxidant receptor 1HD2 was done by molecular docking. The results of the ADME (Absorption, Distribution, Metabolism, and Excretion) showed that these drug candidates are orally bioavailable and have high gastrointestinal absorption and good permeability. Molecular dynamics was used at 100 ns to study the stability of the MA‐1HD2 and Pr5‐1HD2 complexes obtained after molecular docking. Using the retrosynthesis approach, we have proposed a pathway for synthesizing the drug candidates. This study provides useful information on the antioxidant activity of isoxazole‐based compounds. [ABSTRACT FROM AUTHOR]