Novel anthraquinone amide derivatives as potential glyoxalase-I inhibitors.

This study aimed to identify novel Glyoxalase-I (Glo-I) inhibitors with potential anticancer properties, focusing on anthraquinone amide-based derivatives. We synthesized a series of these derivatives and conducted in silico docking studies to predict their binding interactions with Glo-I. In vitro assessments were performed to evaluate the anti-Glo-I activity of the synthesized compounds.

Unraveling Potential Glyoxalase-I Inhibitors Utilizing Structure-Based Drug Design Techniques.

Background: Glyoxalase system detoxifies methylglyoxal and other ketoaldehydes to produce innocuous metabolites that allow the cells to function normally. Its inhibition in cancer cells causes these toxic metabolites to accumulate, and the cancer cells enter the apoptotic stage.

Methods: The techniques of Computer-Aided Drug Design (CADD) were used, and the compounds possessing a zinc-binding group from commercial databases were extracted, using the pharmacophore search protocol.

Computational fragment-based drug design of potential Glo-I inhibitors.

In this study, a fragment-based drug design approach, particularly drug design, was implemented utilising three different crystal structures in order to discover new privileged scaffolds against glyoxalase-I enzyme as anticancer agents. The fragments were evoluted to indicate potential inhibitors with high receptor affinities. The resulting compounds were served as a benchmark for choosing similar compounds from the ASINEX® database by applying different computational ligand-based drug design techniques.

The practice of defensive medicine among Jordanian physicians: A cross sectional study.

Background: Defensive medicine (DM) is a deviation from medical practice that is induced primarily by a threat of liability. While the DM behavior is well studied in the developed countries, little is known in developing countries and never been evaluated in Jordan.

Objective: To evaluate the prevalence of DM practice in Jordan among physicians and to investigate reasons behind its practice and potential strategies to alleviate this practice.

Computational medicinal chemistry role in clinical pharmacy education: Ingavirin for coronavirus disease 2019 (COVID-19) discovery model.

Objective: Given the major shift to patient-directed education, novel coronavirus (nCoV) provides a live example on how medicinal chemistry could be a key science to teach pharmacy students. In this paper, students and clinical pharmacy practitioners will find a stepwise primer on identifying new potential nCoV treatments mechanistically modulated through angiotensin-converting enzyme 2 (ACE2).

Methods: First, we identified the maximum common pharmacophore between carnosine and melatonin as background ACE2 inhibitors.

Marine-Based Candidates as Potential RSK1 Inhibitors: A Computational Study.

Manzamines are chemically related compounds extracted from the methanolic extract of species. Seven compounds were identified by our research group and are being characterized. As their biological target is unknown, this work is based on previous screening work performed by Mayer et al.

and Investigation of Anti Activity of Selected Phytochemicals.

Introduction: is Gram-negative helical bacteria that inhibit stomach mucosal lining and establish infection. Urease enzyme was confirmed to be pivotal target in which its suppression will prompt bacteria treatment and eradication.

Methods: Series of naturally bioactive compounds were selected based on ethnobotanical and molecular modeling techniques with potential urease inhibitory effect.

Design, Synthesis and Biological Evaluation of 1,4-Benzenesulfonamide Derivatives as Glyoxalase I Inhibitors.

Background: Glyoxalase system is one of the defense cellular mechanisms that protect cells against endogenous harmful metabolites, mainly methylglyoxal (MG), through conversion of cytotoxic methylglyoxal into the non-toxic lactic acid. Glyoxalase system comprises of two enzymes glyoxalase I, glyoxalase II, and a catalytic amount of reduced glutathione. Cancerous cells overexpress glyoxalase I, making it a target for cancer therapy.

Lead optimization and biological evaluation of diazenylbenzenesulfonamides inhibitors against glyoxalase-I enzyme as potential anticancer agents.

In a previous report, we described the discovery of (E)-5-((8-hydroxyquinolin-5-yl)diazenyl)-2-methylbenzenesulfonamide as a potent inhibitor of GLO-I enzyme with IC of 1.28 ± 0.12 μM.

An Ethical Roadmap for Prioritizing Medical Resources Within Muslim Societies During the COVID-19 Pandemic.

Profound ethical challenges have been generated by the emergence of the COVID-19 pandemic. The unprecedented plights that have arisen have led nations to devise ethical roadmaps for handling their finite resources. Muslim countries are no exception and must continue to endure the effects of the pandemic, as more waves of infections from new strains are being reported.

Identification of the First "Two Digit Nano-molar" Inhibitors of the Human Glyoxalase-I Enzyme as Potential Anticancer Agents.

Background: Glyoxalase-I (Glo-I) enzyme is recognized as an indispensable druggable target in cancer treatment. Its inhibition will lead to the accumulation of toxic aldehyde metabolites and cell death. Paramount efforts were spent to discover potential competitive inhibitors with the aim to eradicate cancer.

The ethics of practicing defensive medicine in Jordan: a diagnostic study.

Background: Defensive medicine (DM) practice refers to the ordering or prescription of unnecessary treatments or tests while avoiding risky procedures for critically ill patients with the aim to alleviate the physician's legal responsibility and preserve reputation. Although DM practice is recognized, its dimensions are still uncertain. The subject has been highly investigated in developed countries, but unfortunately, many developing countries are unable to investigate it properly.

Molecular docking and dynamic studies of a potential therapeutic target inhibiting glyoxalase system: Metabolic action of the 3, 3 '- [3- (5-chloro-2-hydroxyphenyl) -3-oxopropane-1, 1-diyl] - Bis-4-hydroxycoumarin leads overexpression of the intracellular level of methylglyoxal and induction of a pro-apoptotic phenomenon in a hepatocellular carcinoma model.

Methylglyoxal is a dicarbonyl compound recruited as a potential cytotoxic marker, initially presents in cells and considered as a metabolite of the glycolytic pathway. Our aim is to demonstrate the inhibitory effect of 3, 3'-[3-(5-chloro-2-hydroxyphenyl)-3-oxopropane-1, 1-diyl] Bis (4-hydroxycoumarin) on the glyoxalase system, and indirectly its anticancer activity. The docking of OT-55 was conducted by using Flexible docking protocol, ChiFlex and libdock tools inside the active site of Glo-I indicated that both hydrogen bonding and hydrophobic interactions contributed significantly in establishing potent binding with the active site which is selected as a strong inhibitor with high scoring values and maximum Gibbs free energy.

Carnosine to Combat Novel Coronavirus (nCoV): Molecular Docking and Modeling to Cocrystallized Host Angiotensin-Converting Enzyme 2 (ACE2) and Viral Spike Protein.

Aims: Angiotensin-converting enzyme 2 (ACE2) plays an important role in the entry of coronaviruses into host cells. The current paper described how carnosine, a naturally occurring supplement, can be an effective drug candidate for coronavirus disease (COVID-19) on the basis of molecular docking and modeling to host ACE2 cocrystallized with nCoV spike protein.

Methods: First, the starting point was ACE2 inhibitors and their structure-activity relationship (SAR).

Ellagic acid: A potent glyoxalase-I inhibitor with a unique scaffold.

The glyoxalase system, particularly glyoxalase-I (GLO-I), has been approved as a potential target for cancer treatment. In this study, a set of structurally diverse polyphenolic natural compounds were investigated as potential GLO-I inhibitors. Ellagic acid was found, computationally and experimentally, to be the most potent GLO-I inhibitor among the tested compounds which showed an IC50 of 0.

Design, synthesis and biological evaluation of novel glyoxalase I inhibitors possessing diazenylbenzenesulfonamide moiety as potential anticancer agents.

The enzyme glyoxalase-I (Glo-I) is an essential therapeutic target in cancer treatment. Significant efforts have been made to discover competitive inhibitors of Glo-I as potential anticancer agents. Herein, we report the synthesis of a series of diazenylbenzenesulfonamide derivatives, their in vitro evaluation against Glo-I and the resulting structure-activity relationships.

Identification of Human Leukotriene A4 Hydrolase Inhibitors Using Structure-Based Pharmacophore Modeling and Molecular Docking.

Leukotriene B4 (LTB4) is a potent, proinflammatory lipid mediator implicated in the pathologies of an array of inflammatory diseases and cancer. The biosynthesis of LTB4 is regulated by the leukotriene A4 hydrolase (LTAH). Compounds capable of limiting the formation of LTB4, through selective inhibition of LTAH, are expected to provide potent anti-inflammatory and anti-cancer agents.

The Ethics of Gene Editing from an Islamic Perspective: A Focus on the Recent Gene Editing of the Chinese Twins.

In light of the development of "CRISPR" technology, new promising advances in therapeutic and preventive approaches have become a reality. However, with it came many ethical challenges. The most recent worldwide condemnation of the first use of CRISPR to genetically modify a human embryo is the latest example of ethically questionable use of this new and emerging field.

Combined High Throughput Screening with QSAR Analysis Unravelling Potential Glyoxalase-I Inhibitors.

Aims: Discovery of new Glo-I inhibitors as potential anticancer agents.

Background: Glyoxalase system is ubiquitous system in human cells which has been examined thoroughly for its role in cancerous diseases. It performs detoxifying endogenous harmful metabolites, mainly methylglyoxal (MG) into non-toxic bystanders.

Discovery of a nanomolar inhibitor of the human glyoxalase-I enzyme using structure-based poly-pharmacophore modelling and molecular docking.

The glyoxalase-I (GLO-I) enzyme, which is the initial enzyme of the glyoxalase system that is responsible for the detoxification of cytotoxic α-ketoaldehydes, such as methylglyoxal, has been approved as a valid target in cancer therapy. Overexpression of GLO-I has been observed in several types of carcinomas, including breast, colorectal, prostate, and bladder cancer. In this work we aimed to identify potential GLO-I inhibitors via employing different structure-based drug design techniques including structure-based poly-pharmacophore modelling, virtual screening, and molecular docking.

Multi-Armed 1,2,3-Selenadiazole and 1,2,3-Thiadiazole Benzene Derivatives as Novel Glyoxalase-I Inhibitors.

Glyoxalase-I (Glo-I) enzyme was established to be a valid target for anticancer drug design. It performs the essential detoxification step of harmful byproducts, especially methylglyoxal. A robust computer-aided drug design approach was used to design and validate a series of compounds with selenium or sulfur based heterorings.

Withania somnifera root powder protects againist post-traumatic stress disorder-induced memory impairment.

Post-traumatic stress disorder (PTSD) is precipitated by exposure to severe traumatic events such as wars, natural disasters, catastrophes, or other traumatic events. Withania somnifera (WS) Dunal (family: Solanaceae) known traditionally as "Ashwaghanda" is used widely in ayurvedic medicine, and known to have positive role in neurodegenerative diseases. In this study, WS effect on impairment of memory due to PTSD was studied in animal models.

Combination of pharmacophore modeling and 3D-QSAR analysis of potential glyoxalase-I inhibitors as anticancer agents.

Glyoxalase system is an ubiquitous system in human cells which has been examined thoroughly for its role in different diseases. It comprises two enzymes; Glyoxalase I (Glo-I) and Glyoxalase II (Glo-II) which perform detoxifying endogenous harmful metabolites, mainly methylglyoxal (MG) into non-toxic bystanders. In silico computer Aided Drug Design approaches were used and ninety two diverse pharmacophore models were generated from eighteen Glyoxalase I crystallographic complexes.

Molecular Dynamics Simulations of Adenosine Receptors: Advances, Applications and Trends.

Adenosine receptors (ARs) are transmembrane proteins that belong to the G protein-coupled receptors (GPCRs) superfamily and mediate the biological functions of adenosine. To date, four AR subtypes are known, namely A1, A2A, A2B and A3 that exhibit different signaling pathways, tissue localization, and mechanisms of activation. Moreover, the widespread ARs and their implication in numerous physiological and pathophysiological conditions had made them pivotal therapeutic targets for developing clinically effective agents.