Synthesis and DPPH scavenging assay of reserpine analogues, computational studies and in silico docking studies in AChE and BChE responsible for Alzheimer's disease

A doença de Alzheimer (DA) é uma doença neurodegenerativado sistema nervoso central, em rápido crescimento, e antioxidantes ajudam a suprimir o estresse oxidativo causado por radicais livres, responsávies pela DA. Avaliou-se, biologicamente, série de derivados sintéticos de indol selecionados para identificar novos antioxidantes. A maioria dos compostos avaliados apresentou de significativa a boa propriedade antioxidante (valor de IC50 399,07140.0 ± 50 µM). Eftuaram-se estudos de Teoria do Funcional de Densidade (DFT) com os compostos e os seus correspondentes radicais livres. As diferenças de energia entre os compostos protótipos e os radicais livres correspondentes proporcionaram boa justificativa para a tendência encontrada nos seus valores de IC50. O ancoramento in silico dos compostos com a acetilcolinesterase (AChE) e com a butirilcolinesterase (BChE), que contribuem para a DA, foi, também, realizado para prever o seu potencial anti-DA.Alzheimer's disease (AD) is a fast growing neurodegenerative disorder of the central nervous system and anti-oxidants can be used to help suppress the oxidative stress caused by the free radicals that are responsible for AD. A series of selected synthetic indole derivatives were biologically evaluated to identify potent new antioxidants. Most of the evaluated compounds showed significant to modest antioxidant properties (IC50 value 399.07 140.0±50 µM). Density Functional Theory (DFT) studies were carried out on the compounds and their corresponding free radicals. Differences in the energy of the parent compounds and their corresponding free radicals provided a good justification for the trend found in their IC50 values. In silico, docking of compounds into the proteins acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), which are well known for contributing in AD disease, was also performed to predict anti-AD potential

Exploration of phenolic acid derivatives as inhibitors of SARS-CoV-2 main protease and receptor binding domain: potential candidates for anti-SARS-CoV-2 therapy

Severe acute respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is the etiological virus of Coronavirus Disease 2019 (COVID-19) which has been a public health concern due to its high morbidity and high mortality. Hence, the search for drugs that incapacitate the virus via inhibition of vital proteins in its life cycle is ongoing due to the paucity of drugs in clinical use against the virus. Consequently, this study was aimed at evaluating the potentials of natural phenolics against the Main protease (Mpro) and the receptor binding domain (RBD) using molecular modeling techniques including molecular docking, molecular dynamics (MD) simulation, and density functional theory (DFT) calculations. To this end, thirty-five naturally occurring phenolics were identified and subjected to molecular docking simulation against the proteins. The results showed the compounds including rosmarinic acid, cynarine, and chlorogenic acid among many others possessed high binding affinities for both proteins as evident from their docking scores, with some possessing lower docking scores compared to the standard compound (Remdesivir). Further subjection of the hit compounds to drug-likeness, pharmacokinetics, and toxicity profiling revealed chlorogenic acid, rosmarinic acid, and chicoric acid as the compounds with desirable profiles and toxicity properties, while the study of their electronic properties via density functional theory calculations revealed rosmarinic acid as the most reactive and least stable among the sets of lead compounds that were identified in the study. Molecular dynamics simulation of the complexes formed after docking revealed the stability of the complexes. Ultimately, further experimental procedures are needed to validate the findings of this study

Apple peels as a potential adsorbent for removal of Cu and Cr from wastewater

Solid waste management (SWM) is one of the biggest concerns of society and agricultural waste is generated in vast amounts. In this study removal of Cu and Cr from wastewater using chemically modified apple peels was studied by following batch sorption experiments. Effects of metal concentration, adsorbent dose, pH, temperature and contact duration on the adsorption of Cu & Cr were investigated by using atomic adsorption spectrophotometer (AAS). SEM & EDX analysis of the adsorbents were recorded to study the morphology of the prepared adsorbents. Qmax value of apple peels is 25 for Cr and 22 for Cu, while for apple peel charcoal it is 33 for Cr and 47 for Cu, for treated apple peels Qmax is 50 for Cr and 52 for Cu adsorption. The data was processed using pseudo first, second order kinetic and intraparticle diffusion. Results depicted that the calculated adsorption capacities (qe cal) were found to be close to the experimental values (qe cal) by following pseudo-second-order kinetics. The applicability of the Langmuir and Freundlich adsorption isotherms was tested. Results showed that the Langmuir model is best fitted on adsorption data because regression factor R2 values are good for the Langmuir model. HIGHLIGHTS This study focuses on efficient removal of Cr and Cu from wastewater using solid waste.; These prepared adsorbents are eco-friendly and non hazardous.; Maximum adsorption capacity (Qmax) up to 50 for Cr and 52 for Cu for treated apple peels is observed.; Calculated adsorption capacities (qe cal) were found to be close to the experimental values (qe cal) by following pseudo-second-order kinetics.

Synthesis and DPPH scavenging assay of reserpine analogues, computational studies and in silico docking studies in AChE and BChE responsible for Alzheimer's disease

Alzheimer's disease (AD) is a fast growing neurodegenerative disorder of the central nervous system and anti-oxidants can be used to help suppress the oxidative stress caused by the free radicals that are responsible for AD. A series of selected synthetic indole derivatives were biologically evaluated to identify potent new antioxidants. Most of the evaluated compounds showed significant to modest antioxidant properties (IC50 value 399.07 140.0±50 µM). Density Functional Theory (DFT) studies were carried out on the compounds and their corresponding free radicals. Differences in the energy of the parent compounds and their corresponding free radicals provided a good justification for the trend found in their IC50 values. In silico, docking of compounds into the proteins acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), which are well known for contributing in AD disease, was also performed to predict anti-AD potential

In vitro modulatory effects of functionalized pyrimidines and piperidine derivatives on Aryl hydrocarbon receptor (AhR) and glucocorticoid receptor (GR) activities

The development of biologically active molecules based on molecular recognition is an attractive and challenging task in medicinal chemistry and the molecules that can activate/deactivate certain receptors are of great medical interest. In this contribution, selected pyrimidine/piperidine derivatives were synthesized and tested for the ability to activate/deactivate Aryl hydrocarbon receptor (AhR) and Glucocorticoid receptor (GR). Tested compounds are shown to activate the receptors but to much lesser extent than positive controls, dioxin and dexamethasone for Ahr and GR, respectively. However, some of them antagonized the positive controls action. Although further in vivo studies are needed to fully characterize the bioactivities of these compounds, the reported in vitro evidences demonstrate that they might be used as the modulators of AhR and GR activities. (C) 2017 Elsevier Inc. All rights reserved