Dioscorea bulbifera seed peel chars as electrocatalysts for hydrogen evolution reactions-experimental and theoretical investigations.

Context: This study presents hydrochars derived from Dioscorea bulbifera seed peel as electrocatalysts for hydrogen evolution reaction (HER). These hydrochars are produced at 150 °C and 200 °C and respectively designated DBP@H_150 and DBP@H_200. FTIR, BET surface area measurement, and Boehm titration were used to characterize these hydrochars.

Malaria parasite cysteine and aspartic proteases as key drug targets for antimalarial therapy.

Context: Cysteine and aspartic proteases are enzyme families that play crucial roles in the life cycle of Plasmodium, the parasite responsible for malaria. These proteases are involved in vital biological processes, such as hemoglobin degradation within the host's red blood cells, protein turnover, and regulation of parasite development. Inhibiting these proteases with small molecule drugs can block the parasite's growth and survival.

A Computational Study of Green Tea Extracts and their Derivatives as Potential Inhibitors for Squalene Monooxygenase.

Background: According to the World Health Organisation, cardiovascular complications have been recognized as the leading course of death between 2000 and 2019. Cardiovascular complications are caused by excess LDL cholesterol in the body or arteries that can build up to form a plaque. There are drugs currently in clinical use called statins that target HMGCoA reductase.

Inhibitory effects of selected cannabinoids against dipeptidyl peptidase IV, an enzyme linked to type 2 diabetes.

Ethnopharmacological Relevance: In recent times the decriminalisation of cannabis globally has increased its use as an alternative medication. Where it has been used in modern medicinal practises since the 1800s, there is limited scientific investigation to understand the biological activities of this plant.

Aim Of The Study: Dipeptidyl peptidase IV (DPP-IV) plays a key role in regulating glucose homeostasis, and inhibition of this enzyme has been used as a therapeutic approach to treat type 2 diabetes.

In Silico Substrate-Binding Profiling for SARS-CoV-2 Main Protease (M) Using Hexapeptide Substrates.

The SARS-CoV-2 main protease (M) is essential for the life cycle of the COVID-19 virus. It cleaves the two polyproteins at 11 positions to generate mature proteins for virion formation. The cleavage site on these polyproteins is known to be Leu-Gln↓(Ser/Ala/Gly).

Rationalising the retro-Diels-Alder fragmentation pattern of viscutins using electrospray interface-tandem mass spectrometry coupled to theoretical modelling.

Rationale: Although mass spectrometry (MS) is a powerful tool in structural elucidation of unknown flavonoids based on their unique fragmentation patterns, proposing the correct fragmentation mechanism is still a challenge from tandem mass spectrometry data only. In recent years, computational tools such as molecular networking and MS2LDA have played a major role in the identification of structurally related compounds through an in-depth survey of their fragmentation patterns.

Methods: Therefore, in this study, three viscutin molecules in Viscum combreticola Engl.

Insights into the Dynamics and Binding of Two Polyprotein Substrate Cleavage Points in the Context of the SARS-CoV-2 Main and Papain-like Proteases.

It is well known that vital enzymes in the replication process of the coronavirus are the SARS-CoV-2 PLpro and SARS-CoV-2 3CLpro, both of which are important targets in the search for anti-coronavirus agents. These two enzymes are responsible for cleavage at various polyprotein sites in the SARS-CoV-2 lifecycle. Herein, the dynamics of the polyprotein cleavage sequences for the boundary between non-structural proteins Nsp1 and Nsp2 (CS1) and between Nsp2 and Nsp3 (CS2) in complex with both the papain-like protein PLpro and the main protease 3CLpro were explored using computational methods.

A multiscale ONIOM study of the buckminsterfullerene (C) Diels-Alder reaction: from model design to reaction path analysis.

The hybrid ONIOM (Our own N-layered Integrated molecular Orbital and molecular Mechanics) formalism is employed to investigate the Diels-Alder reaction of the buckminsterfullerene C. Our computations suggest that the ONIOM2(M06-2X/6-31G(d): SVWN/STO-3G) model, enclosing both the diene and the pyracyclene fragment of C60 in the higher-layer, provides a reasonable trade-off between accuracy and computational cost as it comes to predicting reaction energetics. Moreover, the frontier molecular orbital (FMO) theory and activation strain model (ASM) are jointly relied on to rationalize the effect of -OH and -CN substituents on the activation barrier of this reaction.

Solvent promoted tautomerism in thione-containing tetraazatricyclics: evidence from H NMR spectroscopy and transition state studies.

Tautomerism in the nitro substituted thione-containing traazatricyclics has been investigated. Evidence from H NMR indicating the existence of the tautomers has been augmented with computational studies providing evidence of the stability or otherwise of these tautomers. The role of water and DMSO in the formation of the tautomers has been explained.

AMADAR: a python-based package for large scale prediction of Diels-Alder transition state geometries and IRC path analysis.

Predicting transition state geometries is one of the most challenging tasks in computational chemistry, which often requires expert-based knowledge and permanent human intervention. This short communication reports technical details and preliminary results of a python-based tool (AMADAR) designed to generate any Diels-Alder (DA) transition state geometry (TS) and analyze determined IRC paths in a (quasi-)automated fashion, given the product SMILES. Two modules of the package are devoted to performing, from IRC paths, reaction force analyses (RFA) and atomic (fragment) decompositions of the reaction force F and reaction force constant [Formula: see text].

The Molecular Basis of the Effect of Temperature on the Structure and Function of SARS-CoV-2 Spike Protein.

The remarkable rise of the current COVID-19 pandemic to every part of the globe has raised key concerns for the current public healthcare system. The spike (S) protein of SARS-CoV-2 shows an important part in the cell membrane fusion and receptor recognition. It is a key target for vaccine production.

New Insights into the (A)Synchronicity of Diels-Alder Reactions: A Theoretical Study Based on the Reaction Force Analysis and Atomic Resolution of Energy Derivatives.

In the present manuscript, we report new insights into the concept of (a)synchronicity in Diels-Alder (DA) reactions in the framework of the reaction force analysis in conjunction with natural population calculations and the atomic resolution of energy derivatives along the intrinsic reaction coordinate (IRC) path. Our findings suggest that the DA reaction transitions from a preferentially concerted mechanism to a stepwise one in a 0.10 Å window of synchronicity indices ranging from 0.

Drug Resistance in the HIV-1 Subtype C Protease Enzyme: A High Throughput Virtual Screening Approach in Search of New Ligands with Activity.

Background: HIV-1 subtype C protease is a strategic target for antiretroviral treatment. However, resistance to protease inhibitors appears after months of treatment. Chromones and 2- biscoumarin derivatives show potential for inhibition of the HIV- subtype C protease.

Force Field Parameters for FeS Clusters of Dihydropyrimidine Dehydrogenase, the 5-Fluorouracil Cancer Drug Deactivation Protein: A Step towards In Silico Pharmacogenomics Studies.

The dimeric dihydropyrimidine dehydrogenase (DPD), metalloenzyme, an adjunct anti-cancer drug target, contains highly specialized 4 × FeS clusters per chain. These clusters facilitate the catalysis of the rate-limiting step in the pyrimidine degradation pathway through a harmonized electron transfer cascade that triggers a redox catabolic reaction. In the process, the bulk of the administered 5-fluorouracil (5-FU) cancer drug is inactivated, while a small proportion is activated to nucleic acid antimetabolites.

Interaction of silver nanoparticles with catechol methyltransferase: Spectroscopic and simulation analyses.

Catechol O-methyltransferase, an enzyme involved in the metabolism of catechol containing compounds, catalyzes the transfer of a methyl group between S-adenosylmethionine and the hydroxyl groups of the catechol. Furthermore it is considered a potential drug target for Parkinson's disease as it metabolizes the drug levodopa. Consequently inhibitors of the enzyme would increase levels of levodopa.

SANCDB: an update on South African natural compounds and their readily available analogs.

Background: South African Natural Compounds Database (SANCDB; https://sancdb.rubi.ru.

Synthesis, Characterization and Biological Activity of Some Dithiourea Derivatives.

Novel dithiourea derivatives have been designed as HIV-1 protease inhibitors using Autodock 4.2, synthesized and characterized by spectroscopic methods and microanalysis. 1-(3-Bromobenzoyl)-3-[2-([(3-bromophenyl)formami-do]methanethioylamino)phenyl]thiourea (10) and 3-benzoyl-1[(phenylformamido)methanethioyl]aminothiourea (12) gave a percentage viability of 17.

Potential repurposing of four FDA approved compounds with antiplasmodial activity identified through proteome scale computational drug discovery and in vitro assay.

Malaria elimination can benefit from time and cost-efficient approaches for antimalarials such as drug repurposing. In this work, 796 DrugBank compounds were screened against 36 Plasmodium falciparum targets using QuickVina-W. Hits were selected after rescoring using GRaph Interaction Matching (GRIM) and ligand efficiency metrics: surface efficiency index (SEI), binding efficiency index (BEI) and lipophilic efficiency (LipE).

Synthesis and anti-parasitic activity of N-benzylated phosphoramidate Mg-chelating ligands.

A series of N-benzylated phosphoramidate esters, containing a 3,4-dihydroxyphenyl Mg-chelating group, has been synthesised in five steps as analogues of fosmidomycin, a Plasmodium falciparum 1-deoxy-1-d-xylulose-5-phosphate reductoisomerase (PfDXR) inhibitor. The 3,4-dihydroxyphenyl group effectively replaces the Mg-chelating hydroxamic acid group in fosmidomycin. The compounds showed very encouraging anti-parasitic activity with IC values of 5.

Synthesis and anti-parasitic activity of achiral N-benzylated phosphoramidic acid derivatives.

Synthetic pathways have been developed to access a series of N-benzylated phosphoramidic acid derivatives as novel, achiral analogues of the established Plasmodium falciparum 1-deoxy-d-xylulose-5-phosphate reductase (PfDXR) enzyme inhibitor, FR900098. Bioassays of the targeted compounds and their synthetic precursors have revealed minimal antimalarial activity but encouraging anti-trypanosomal activity - in one case with an IC value of 5.4 µM against Trypanosoma brucei, the parasite responsible for Nagana (African cattle sleeping sickness).

Seed Extract of and Its Constituent Bakuchiol Impairs AHL-Based Quorum Sensing and Biofilm Formation in Food- and Human-Related Pathogens.

The emergence of multi-drug resistance in pathogenic bacteria in clinical settings as well as food-borne infections has become a serious health concern. The problem of drug resistance necessitates the need for alternative novel therapeutic strategies to combat this menace. One such approach is targeting the quorum-sensing (QS) controlled virulence and biofilm formation.

Iron(iii)porphyrin electrocatalyzed enantioselective carbon-chloride bond cleavage of hexachlorocyclohexanes (HCHs): combined experimental investigation and theoretical calculations.

Enantioselective electrocatalysis of α-, β-, γ- and δ-hexachlorocyclohexanes (HCHs) by tetrakis-pentafluorophenyl-Fe(iii)porphyrin is described. The first example of the combined use of electrochemical measurements and theoretical calculations to determine the mechanism of the enantioselective C-Cl bond cleavage of the electrocatalysis is reported. The electrochemical measurements demonstrate that the reactivity of the HCHs follows the order γ-HCH > α-HCH > δ-HCH > β-HCH.

High throughput screening, docking, and molecular dynamics studies to identify potential inhibitors of human calcium/calmodulin-dependent protein kinase IV.

Calcium/calmodulin-dependent protein kinase IV (CAMKIV) is associated with many diseases including cancer and neurodegenerative disorders and thus being considered as a potential drug target. Here, we have employed the knowledge of three-dimensional structure of CAMKIV to identify new inhibitors for possible therapeutic intervention. We have employed virtual high throughput screening of 12,500 natural compounds of Zinc database to screen the best possible inhibitors of CAMKIV.

Unravelling the unfolding mechanism of human integrin linked kinase by GdmCl-induced denaturation.

Integrin-linked kinase (ILK) is a ubiquitously expressed Ser/Thr kinase which plays significant role in the cell-matrix interactions and growth factor signalling. In this study, guanidinium chloride (GdmCl)-induced unfolding of kinase domain of ILK (ILK) was carried out at pH 7.5 and 25 °C.