Cheminformatics-aided discovery of potential allosteric site modulators of ubiquitin-specific protease 7.

Ubiquitin-specific peptidase 7 (USP7) is a deubiquitinating enzyme that mediates the stability and activity of numerous proteins. At basal expression levels, USP7 stabilizes p53 protein, even in the presence of excess MDM2. However, its overexpression leads to the deubiquitination of MDM2 at a rate faster than p53, leading to p53 degradation and pro-tumorigenic roles.

The Anti-Leukemic Activities of Campesterol and Α-Tocopherol Against BCL-2 Target through Computational Drug Design Approaches.

Introduction: Heterogeneous Acute Myeloid Leukemia (AML) causes substantial worldwide morbidity and death. AML is characterized by excessive proliferation of immature myeloid cells in the bone marrow and impaired apoptotic regulator expression.

Method: B-Cell Lymphoma 2 (BCL-2), an anti-apoptotic protein overexpressed in AML, promotes leukemic cell survival and chemoresistance.

Predictive identification and design of potent inhibitors targeting resistance-inducing candidate genes from whole-genome sequences.

This work utilizes predictive modeling in drug discovery to unravel potential candidate genes from that are implicated in antimicrobial resistance; we subsequently target the gidB, MacB, and KatG genes with some compounds from plants with reported antibacterial potentials. The resistance genes and plasmids were identified from 10 whole-genome sequence datasets of ; forty two plant compounds were selected, and their 3D structures were retrieved and optimized for docking. The 3D crystal structures of KatG, MacB, and gidB were retrieved and prepared for molecular docking, molecular dynamics simulations, and ADMET profiling.

Effect of curcumin-donepezil combination on spatial memory, astrocyte activation, and cholinesterase expressions in brain of scopolamine-treated rats.

Background: The study investigated the effect of co-administration of curcumin and donepezil on several markers of cognitive function (such as spatial memory, astrocyte activation, cholinesterase expressions) in the brain cortex and hippocampus of scopolamine-treated rats.

Method And Results: For seven consecutive days, a pre-treatment of curcumin (50 mg/kg) and/or donepezil (2.5 mg/kg) was administered.

Computer-aided drug discovery of c-Abl kinase inhibitors from plant compounds against chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a hematological malignancy characterized by the neoplastic transformation of hematopoietic stem cells, driven by the Philadelphia (Ph) chromosome resulting from a translocation between chromosomes 9 and 22. This Ph chromosome harbors the breakpoint cluster region (BCR) and the Abelson (ABL) oncogene (BCR-ABL1) which have a constitutive tyrosine kinase activity. However, the tyrosine kinase activity of BCR-ABL1 have been identified as a key player in CML initiation and maintenance through c-Abl kinase.

HPLC/ESI-MS Characterization of Phenolic Compounds from Cnicus benedictus L. Roots: A Study of Antioxidant, Antibacterial, Anti-Inflammatory, and Anti-Alzheimer's Activity.

The phenolic composition of Cnicus benedictus roots from four Algerian regions was investigated. Extractions were performed in both hydro-methanolic (30 : 70, v/v) and hydro-ethanolic (30 : 70, v/v) solvents. Their efficiency was determined in terms of the qualitative and quantitative composition in phenolic compounds by HPLC-LC/MS of the different extracts isolated from C.

An integrative computational approach for the identification of dual inhibitors of isocitrate dehydrogenase 1 and 2 from phytocompounds of .

Genetic alterations of the genes encoding the isocitrate dehydrogenase (IDH) enzymes have been identified in about 20% of acute myeloid leukemia (AML) cases as well as many other forms of cancers. Notable among these alterations are the neomorphic IDH1_R132H and IDH2_R140Q mutations which lead to the production of an oncometabolite. Hence, their inhibition is widely considered a therapeutic strategy in the treatment of many cancers.

You must be flexible enough to be trained, Mr. Dynamics simulator.

This article highlights two major problems associated with molecular dynamics studies: poor parameterization of systems and misleading interpretation of data. To address these issues, we advocate for meticulous system parameterization and careful interpretation of statistics within the framework of the study system, with a focus on high-quality and rigorous simulations. Our letter aims to encourage the adoption of the best practices in the field.

Repurposing the inhibitors of MMP-9 and SGLT-2 against ubiquitin specific protease 30 in Parkinson's disease: computational modelling studies.

Ubiquitin specific protease 30 (USP30) has been attributed to mitochondrial dysfunction and impediment of mitophagy in Parkinson's disease (PD). This happens once ubiquitin that supposed to bind with deformed mitochondria at the insistence of Parkin, it's been recruited by USP30 the distal ubiquitin binding domain. This is a challenge when PINK1 and Parkin loss their functions due to mutation.

Computer-aided analysis of quercetin mechanism of overcoming docetaxel resistance in docetaxel-resistant prostate cancer.

Background: Prostate cancer (PC) is a silent but potent killer among men. In 2018, PC accounted for more than 350, 000 death cases while more than 1.2 million cases were diagnosed.

Identification of a 1, 8-naphthyridine-containing compound endowed with the inhibition of p53-MDM2/X interaction signaling: a computational perspective.

Various studies have established that molecules specific for MDMX inhibition or optimized for dual inhibition of p53-MDM2/MDMX interaction signaling are more suitable for activating the Tp53 gene in tumor cells. Nevertheless, there are sparse numbers of approved molecules to treat the health consequences brought by the lost p53 functions in tumor cells. Consequently, this study explored the potential of a small molecule ligand containing 1, 8-naphthyridine scaffold to act as a dual inhibitor of p53-MDM2/X interactions using computational methods.

In silico molecular modeling and simulations of black tea theaflavins revealed theaflavin-3'-gallate as putative liver X receptor-beta agonist.

The low constitutive activation of Liver X receptor, an endogenous nuclear receptor with two subtypes (α and β), is a condition lying at the crossroad of cancer and cardiovascular disease. Both natural and synthetic Liver X receptor agonists have reportedly shown remarkable antiproliferative and atheroprotective effects but the repeated doses of its synthetic ones are also paradoxically associated with hyperlipidaemic effects and neurotoxicity, though attributed to the alpha subtype. This highlights the need for novel, safe, and potent LXR-beta-selective agonists.

study revealed the inhibitory activity of selected phytomolecules of against VacA implicated in gastric ulcer.

Gastric ulcer is associated with weakening of the mucous coating of the stomach and damages to the intestinal lining. It is caused by assisted by enzymes including VacA, which necessitates the need for inhibitors of VacA. Bioactive compounds from have been documented to have anti-inflammatory activities.

Computational Investigation of 1, 3, 4 Oxadiazole Derivatives as Lead Inhibitors of VEGFR 2 in Comparison with EGFR: Density Functional Theory, Molecular Docking and Molecular Dynamics Simulation Studies.

Vascular endothelial growth factor (VEGF) is an angiogenic factor involved in tumor growth and metastasis. Gremlin has been proposed as a novel therapeutic pathway for the treatment of renal inflammatory diseases, acting via VEGFR 2 receptor. To date, most FDA-approved tyrosine kinase (TK) inhibitors have been reported as dual inhibitors of EGFR and VEGFR 2.

Designing a vaccine-based therapy against Epstein-Barr virus-associated tumors using immunoinformatics approach.

Epstein-Barr virus (EBV) is widely known due to its role in the etiology of infectious mononucleosis. However, it is the first oncovirus that was identified and has been implicated in the etiology of several types of cancers. Globally, EBV infection is associated with more than 200, 000 new cancer cases and 150, 000 deaths yearly.

Discovery of Novel HSP27 Inhibitors as Prospective Anti-Cancer Agents Utilizing Computer-Assisted Therapeutic Discovery Approaches.

Heat shock protein 27 (HSP27) is a protein that works as a chaperone and an antioxidant and is activated by heat shock, environmental stress, and pathophysiological stress. However, HSP27 dysregulation is a characteristic of many human cancers. HSP27 suppresses apoptosis and cytoskeletal reorganization.

Mistletoe infested and leaves supplemented diet enhances antioxidant and insulin-like peptide mRNA levels in .

Moringa and Almond are common plants of medicinal and economic value which are often infested with mistletoe. Host plants' infestation could result in major differences in their phytoconstituents and biological activities. Thus, effects of mistletoe infestation on Moringa and Almond host plants supplemented diets on mRNA expression levels of insulin-like peptide-2 (), heat shock protein-70 () and superoxide dismutase () in diabetic-like flies were evaluated using quantitative real-time PCR system.

In Silico Prospects and Therapeutic Applications of Ouabagenin and Hydroxylated Corticosteroid Analogues in the Treatment of Lung Cancer.

Lung cancer is the second most prevalent carcinoma around the world, and about 80% of patients are of non-small cell lung cancer (NS-CLC). Epidermal growth factor receptor (EGFR) is the most expressed protein kinases in lung cancer and hence can be used in target-related anti-cancer therapy. Here, computational approach is used for the exploration of the anti-cancer potential of new steroid derivatives as previously no in vitro data was available for them.

Hesperetin protects against diesel exhaust particles-induced cardiovascular oxidative stress and inflammation in Wistar rats.

Air particulate matter exposure has been linked to cardiovascular and atherosclerosis as a result of increase oxidative stress and inflammatory response. This study aims to determine the effect of the use of hesperetin (HESP) as a therapeutic agent to mitigate the cardiovascular oxidative and pro-inflammatory effects of diesel exhaust particles in Wistar rats. DEP was collected from an Iveco cargo engine truck, and n-hexane fraction (hDEP) was obtained.

Will Africans take COVID-19 vaccination?

The economic and humanistic impact of COVID-19 pandemic is enormous globally. No definitive treatment exists, hence accelerated development and approval of COVID-19 vaccines, offers a unique opportunity for COVID-19 prevention and control. Vaccine hesitancy may limit the success of vaccine distribution in Africa, therefore we assessed the potentials for coronavirus vaccine hesitancy and its determinants among Africans.

Molecular docking and pharmacokinetic studies of phytocompounds from Nigerian Medicinal Plants as promising inhibitory agents against SARS-CoV-2 methyltransferase (nsp16).

Background: Since the index case was reported in China, COVID-19 has led to the death of at least 4 million people globally. Although there are some vaccine cocktails in circulation, the emergence of more virulent variants of SARS-CoV-2 may make the eradication of COVID-19 more difficult. Nsp16 is an S-adenosyl-L-Methionine-dependent methyltransferase that plays an important role in SARS-CoV-2 viral RNA cap formation-a crucial process that confers viral stability and prevents virus detection by cell innate immunity mechanisms.

Fig (Ficus exasperata and Ficus asperifolia)-Supplemented diet improves sexual function, endothelial nitric oxide synthase and suppresses tumour necrosis factor-alpha genes in hypertensive rats.

We measured the effect of varieties of Fig leaves, Ficus exasperata Vahl. (FE) and Ficus asperifolia Miq (FA), commonly found in Sub-sahara Africa for managing hypertension on sexual performance in hypertensive rats, which is unknown. Hypertensive rats experienced erectogenic damage after exposure to 40 mg kg  bw , N(G)-nitro-l-arginine-methyl-ester (L-NAME).

Novel Molecules derived from 3-O-(6-galloylglucoside) inhibit Main Protease of SARS-CoV 2 In Silico.

Unlabelled: The ongoing pandemic caused by the severe acute respiratory syndrome 2 (SARS-CoV 2) has led to more than 168 million confirmed cases with 3.5 million deaths as at 28th May, 2021 across 218 countries. The virus has a cysteine protease called main protease (Mpro) which is significant to it life cycle, tagged as a suitable target for novel antivirals.