High-throughput computational screening for identification of potential hits against bacterial Acriflavine resistance protein B (AcrB) efflux pump.

Antibiotic resistance is a pressing global health challenge, driven in part by the remarkable efflux capabilities of efflux pump in AcrB (Acriflavine Resistance Protein B) protein in Gram-negative bacteria. In this study, a multi-approached computational screening strategy encompassing molecular docking, absorption, distribution, metabolism, excretion and toxicity (ADMET) analysis, druglikeness assessment, molecular dynamics simulations and density functional theory studies was employed to identify novel hits capable of acting against AcrB-mediated antibiotic resistance. Ligand library was acquired from the COCONUT database.

Exploring α, β-unsaturated carbonyl compounds against bacterial efflux pumps computational approach.

Antibiotic resistance has become a pressing global health crisis, with bacterial infections increasingly difficult to treat due to the emergence of multidrug resistance. This study aims to identify potential chalcone molecules that interact with two key multidrug efflux pumps, AcrB and EmrD, of Escherichia coli, using advanced computational tools. ADMET (absorption, distribution, metabolism, excretion, and toxicity), drug-likeness prediction, molecular docking, and molecular dynamics simulation analyses were conducted on a ligand library comprising 100 chalcone compounds against AcrB (PDB: 4DX5) and EmrD (PDB: 2GFP).

Identification of potential biogenic chalcones against antibiotic resistant efflux pump (AcrB) via computational study.

The cases of bacterial multidrug resistance are increasing every year and becoming a serious concern for human health. Multidrug efflux pumps are key players in the formation of antibiotic resistance, which transfer out a broad spectrum of drugs from the cell and convey resistance to the host. Efflux pumps have significantly reduced the efficacy of the previously available antibiotic armory, thereby increasing the frequency of therapeutic failures.

Exploration of limonoids for their broad spectrum antiviral potential DFT, molecular docking and molecular dynamics simulation approach.

Limonoids serve as vital secondary metabolites. Citrus limonoids show a wide range of pharmacological potential. As a result of which limonoids from citrus are of considerable research interest.

Exploring biogenic chalcones as DprE1 inhibitors for antitubercular activity via in silico approach.

Cases of drug-resistant tuberculosis (TB) have increased worldwide in the last few years, and it is a major threat to global TB control strategies and the human population. Mycobacterium tuberculosis is a common causative agent responsible for increasing cases of TB and as reported by WHO, approximately, 1.5 million death occurred from TB in 2020.

Computational Exploration of Anti-cancer Potential of Flavonoids against Cyclin-Dependent Kinase 8: An Molecular Docking and Dynamic Approach.

Over the centuries, cancer has been considered one of the significant health threats. It holds the position in the list of deadliest diseases over the globe. In women, breast cancer is the most common among many cancers and is the second most common cancer all over the world, while lung cancer is the first.

Development of lipoprotein-drug conjugates for targeted drug delivery.

Tumour targeting approaches used in cancer chemotherapy offers prolonged, localized, and protected drug interaction with the diseased tissue with minimal side effects and systemic toxicity, which are accountable for the failure of chemotherapy using conventional delivery systems. The purpose of the present study is to develop an anticancer targeted drug delivery system using synthesized lipoproteins with the integration of quality by design approach. Lipoprotein structures were designed, and quality by design approach was implemented to select variables for optimization.

Identification and Investigation of Chalcone Derivatives as Calcium Channel Blockers: Pharmacophore Modeling, Docking Studies, In vitro Screening, and 3D-QSAR Analysis.

Background: The chalcones were reported to have many biological activities by showing affinity towards many enzymatic targets. The effect of nitric oxide (NO) on calcium channel was extensively studied in different animals; the study was also carried out for NO donor drug and its effect on calcium channel. Till date, the inhibition of calcium channel is of prime importance in the medicinal chemistry to discover newer vascular smooth muscle relaxant drugs.

Optimization of Thiazolidone Scaffolds Using Pocket Modeling for Development of Potential Secretory System Inhibitors of .

Objectives: is the causative organism of tuberculosis, which is the most lethal disease after cancer in the current decade. The development of multidrug and broadly drug-resistant strains is making the problem of tuberculosis more and more critical. In the last 40 years, only one molecule has been added to the treatment regimen.

Computer Assisted Models for Blood Brain Barrier Permeation of 1, 5-Benzodiazepines.

Aim: To generate and validate predictive models for blood-brain permeation (BBB) of CNS molecules using the QSPR approach.

Background: Prediction of molecules crossing BBB remains a challenge in drug delivery. Predictive models are designed for the evaluation of a set of preclinical drugs which may serve as alternatives for determining BBB permeation by experimentation.

Vasorelaxant Effect of Novel Nitric Oxide-Hydrogen Sulfide Donor Chalcone in Isolated Rat Aorta: Involvement of cGMP Mediated sGC and Potassium Channel Activation.

Background And Objective: Recently, nitric oxide (NO) and hydrogen sulfide (H2S) donating moieties were extensively studied for their role in the vasculature as they are responsible for many cellular and pathophysiological functioning. The objective of the present study is to evaluate novel NO and H2S donating chalcone moieties on isolated rat aorta for vasorelaxation, and to investigate the probable mechanism of action.

Methods: To extend our knowledge of vasorelaxation by NO and H2S donor drugs, here we investigated the vasorelaxing activity of novel NO and H2S donating chalcone moieties on isolated rat aorta.

Development of 'S', 'N' Heterocycles as Antimycobacterials Targeting Fatty Acid Biosynthesis.

Background: Mycobacterium tuberculosis is a causative organism of tuberculosis, which is the most deadly disease after cancer in the current decade. The development of multidrug and broadly drug- resistant strains makes the tuberculosis problem more and more critical. In the last 40 years, only one molecule is added to the treatment regimen.

Multi-Targeted Design and Development of Dihydroisoquinolines as Potent Antimalarials.

Background: Malaria is a serious parasitic infection with greater morbidity and motility in recent decades. Cysteine protease and DHODH enzyme serve as a potential target for antimalarial agents which inhibit parasite multiplication in the erythrocyte stage. Development of new leads which specifically target cysteine protease and DHODH enzyme can reduce the side effects and overcome multidrug resistance.

Investigation of anti-inflammatory, nitric oxide donating, vasorelaxation and ulcerogenic activities of 1, 3-diphenylprop-2-en-1-one derivatives in animal models.

The main aim of this work is to find out novel chemical moieties with potent anti-inflammatory and vasorelaxant activities with reduced gastric toxicities. For fulfilling the above aim, here we investigated novel chalcones (1, 3-diphenylprop-2-en-1-one derivatives) with nitric oxide (NO) and hydrogen sulphide (H S) donating potency for anti-inflammatory activity by carrageenan-induced rat paw oedema. These molecules then further evaluated for in-vitro NO-releasing potency and vasorelaxation effect on isolated adult goat aortic tissue.