Exploring the potential of 2-arylbenzimidazole scaffolds as novel α-amylase inhibitors: QSAR, molecular docking, simulation and pharmacokinetic studies.

Previous studies have shown that 2-arylbenzimidazole derivatives have a strong anti-diabetic effect. To further explore this potential, we develop new analogues of the compound using ligand-based drug design and tested their inhibitory and binding properties through QSAR analyses, molecular docking, dynamic simulations and pharmacokinetic studies. By using quantitative structure activity relationship and ligand-based modification, a highly precise predictive model and design of potent compounds was developed from the derivatives of 2-arylbenzimidazoles.

Identification of estrogen receptor agonists among hydroxylated polychlorinated biphenyls using classification-based quantitative structure-activity relationship models.

Identification of estrogen receptor (ER) agonists among environmental toxicants is essential for assessing the potential impact of toxicants on human health. Using 2D autocorrelation descriptors as predictor variables, two binary logistic regression models were developed to identify active ER agonists among hydroxylated polychlorinated biphenyls (OH-PCBs). The classifications made by the two models on the training set compounds resulted in accuracy, sensitivity and specificity of 95.

Activity prediction, structure-based drug design, molecular docking, and pharmacokinetic studies of 1,4-dihydropyridines derivatives as α-amylase inhibitors.

Objectives: Diabetes places a substantial economic burden on countries worldwide. The costs associated with diabetes management, including healthcare services, medications, monitoring equipment, and productivity losses, are substantial. The International Diabetes Federation has estimated that global healthcare expenditures associated with diabetes and its complications exceed hundreds of billions of dollars annually.

Chemo-informatics applications in the design of novel 7-keto-sempervirol derivatives as SmCB1 inhibitors with potential for treatment of Schistosomiasis.

The quest for a sound treatment on the vulnerable population suffering and dying as a result of the blood flukes, S. mansoni is on the increase because both Praziquantel and Oxamniquine widely used for the treatment of Schistosomiasis for over 51 years suffer resistance and recurrence. Here-in, chemo-informatics techniques such as QSAR modeling, pharmacokinetic, docking alongside MD simulation were harnessed in designing novel 7-keto- sempevirolsempevirol derivatives that are more competent against S.

Homology modeling, docking, and ADMET studies of benzoheterocyclic 4-aminoquinolines analogs as inhibitors of .

Objectives: The ongoing fight against endemic diseases is necessary due to the growing resistance of malarial parasites to widely accessible medications. Thus, there has been an ongoing search for antimalarial medications with improved efficacy. The goal of this study was to develop derivatives of benzoheterocyclic 4-aminoquinolines with enhanced activities and better binding affinities than the original compounds.

Development and Validation of Predictive Quantitative Structure-Activity Relationship Models for Estrogenic Activities of Hydroxylated Polychlorinated Biphenyls.

Disruption of the endocrine system by hydroxylated polychlorinated biphenyls (OH-PCBs) is hypothesized, among other potential mechanisms, to be mediated via nuclear receptor binding. Due to the high cost and lengthy time required to produce high-quality experimental data, empirical data to support the nuclear receptor binding hypothesis are in short supply. In the present study, two quantitative structure-activity relationship models were developed for predicting the estrogenic activities of OH-PCBs.

Virtual screening and molecular dynamic simulations of the antimalarial derivatives of 2-anilino 4-amino substituted quinazolines docked against a -DHODH protein target.

Background: The processes of drug development and validation are too expensive to be subjected to experimental trial and errors. Hence, the use of the insilico approach becomes imperative. To this effect, the drug-likeness and pharmacokinetic properties of the ten (10) previously designed derivatives of 2-anilino 4-amino substituted quinazolines were carried out.

Application of QSAR Method in the Design of Enhanced Antimalarial Derivatives of Azetidine-2-carbonitriles, their Molecular Docking, Drug-likeness, and SwissADME Properties.

The resistance of the P. falciparum strain to some of the antimalarial drugs has been a dominant dilemma facing the treatment of this fetid disease. This necessitates the detection and development of new antimalarial agents targeting the P.

prediction of nuclear receptor binding to polychlorinated dibenzofurans and its implication on endocrine disruption in humans and wildlife.

Polychlorinated dibenzofurans (PCDFs) are known to cause endocrine disruption in humans and wildlife but the mechanisms underlying this disruption have not been adequately investigated. In this paper, the susceptibility of the endocrine system to disruption by PCDF congeners via nuclear receptor binding was studied using molecular docking simulation. Findings revealed that some PCDF congeners exhibit high probabilities of binding to androgen receptor in its agonistic and antagonistic conformations.

A computational insight into endocrine disruption by polychlorinated biphenyls via non-covalent interactions with human nuclear receptors.

Production of polychlorinated biphenyls (PCBs) was banned a long time ago because of their harmful health effects but humans continue to be exposed to residual PCBs in the environment. In this study, the susceptibility of human nuclear receptors to binding by PCBs was investigated using molecular docking simulation. Findings revealed that PCBs belonging to ortho-substituted, mono-ortho-substituted and non-ortho-substituted congeners could bind to agonistic conformations of androgen (AR), estrogen (ER α and ER β), glucocorticoid (GR) and thyroid hormone (TR α and TR β) receptors as well as antagonistic conformation of androgen receptor (AR an) but only ortho-substituted and mono-ortho-substituted PCBs could bind to estrogen receptors in their antagonistic conformations (ER α an and ER β an).

Molecular modeling and design of some β-amino alcohol grafted 1,4,5-trisubstituted 1,2,3-triazoles derivatives against chloroquine sensitive, 3D7 strain of .

Resistance nature of () to the most effective antimalarial drug, Artemisinin, intimidate the global goal of total eradication of malarial. In an attempt to overcome this challenge, the research was aimed at designing derivatives of β-amino alcohol grafted 1,4,5-trisubstituted 1,2,3-triazoles with improve activity against the through structural modifications of the most active compound (design template), and their activity determined using the developed theoretical predictive model. To achieve this, the geometries were optimized via density functional theory (DFT) using B3LYP/6-31G basis set to generate molecular descriptors for model development.

Theoretical study on endocrine disrupting effects of polychlorinated dibenzo-p-dioxins using molecular docking simulation.

Polychlorinated dibenzo-p-dioxins (PCDDs) are hypothesized to exert their toxic effects in wildlife and humans via endocrine disruption. However, very scanty information is available on the underlying molecular interactions that trigger this disruption. In this study, molecular docking simulation was used to predict the susceptibility of 12 nuclear receptors to disruption via PCDD bindings.

Free radical scavenging mechanism of 1,3,4-oxadiazole derivatives: thermodynamics of O-H and N-H bond cleavage.

The thermodynamics of free radical scavenge of 1,3,4-oxadiazole derivatives towards oxygen-centred free radicals were investigated by the density functional theory (DFT) method in the gas phase and aqueous solution. Three mechanisms of free radical scavenge namely, hydrogen atom transfer (HAT), single electron transfer followed by proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET) were considered. The antioxidant descriptors that characterize these mechanisms such as, bond dissociation enthalpy (BDE), adiabatic ionization potential (AIP), proton dissociation enthalpy (PDE), proton affinity (PA) and electron transfer enthalpy (ETE) were evaluated.

Evaluation of the antioxidant properties of curcumin derivatives by genetic function algorithm.

The prevalence of degenerative diseases in recent time has triggered extensive research on their control. This condition could be prevented if the body has an efficient antioxidant mechanism to scavenge the free radicals which are their main causes. Curcumin and its derivatives are widely employed as antioxidants.

Mechanism and rate constant of proline-catalysed asymmetric aldol reaction of acetone and p-nitrobenzaldehyde in solution medium: Density-functional theory computation.

In search of new ways to improve catalyst design, the current research focused on using quantum mechanical descriptors to investigate the effect of proline as a catalyst for mechanism and rate of asymmetric aldol reaction. A plausible mechanism of reaction between acetone and 4-nitrobenzaldehyde in acetone medium was developed using highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies calculated via density functional theory (DFT) at the 6-31G∗/B3LYP level of theory. New mechanistic steps were proposed and found to follow, with expansion, the previously reported iminium-enamine route of typical class 1 aldolase enzymes.