Purification and characterization of arginine deiminase from Pseudomonas putida: Structural insights of the differential affinities of l-arginine analogues.

Arginine deiminase (ADI) from Pseudomonas putida was purified using ammonium sulphate precipitation, anion exchange and hydrophobic interaction chromatography. Influence of various chemical compounds (metal ions, reducing agents, sulphydryl agents, and surfactants) on the catalytic activity of ADI was determined was evaluated on the purified ADI. The enzyme displayed high sensitivity towards thiol binding metal ions, chemicals acting on sulfhydryl group, and most of the surfactants.

Identification of leads for antiproliferative activity on MDA-MB-435 human breast cancer cells through pharmacophore and CYP1A1-mediated metabolism.

CYP1A1 is a potential target for anticancer drug development due to its overexpression in certain cancer cells and role in cancer progression. To identify new leads for CYP1A1 mediated anticancer action, we attempted ligand based pharmacophore mapping, virtual screening of databases, molecular docking, MetaSite based filtering, and molecular dynamics simulations. Initial computational and in vitro screening identified 11 compounds from which we identified two lead compounds, ZINC33468944 and ZINC32101539, showed potential antitumor activity on MDA-MB-435 cell lines (GI50 < 0.

Classification of Human Pregnane X Receptor (hPXR) Activators and Non-Activators by Machine Learning Techniques: A Multifaceted Approach.

The Human Pregnane X Receptor (hPXR) is a regulator of drug metabolising enzymes (DME) and efflux transporters (ET). The prediction of hPXR activators and non-activators has pharmaceutical importance to predict the multiple drug resistance (MDR) and drug-drug interactions (DDI). In this study, we developed and validated the computational prediction models to classify hPXR activators and non-activators.

Characterization of differences in substrate specificity among CYP1A1, CYP1A2 and CYP1B1: an integrated approach employing molecular docking and molecular dynamics simulations.

Recent trends in new drug discovery of anticancer drugs have made oncologists more aware of the fact that the new drug discovery must target the developing mechanism of tumorigenesis to improve the therapeutic efficacy of antineoplastic drugs. The drugs designed are expected to have high affinity towards the novel targets selectively. Current research highlights overexpression of CYP450s, particularly cytochrome P450 1A1 (CYP1A1), in tumour cells, representing a novel target for anticancer therapy.

Pregnane X Receptor and P-glycoprotein: a connexion for Alzheimer's disease management.

The translational failure between preclinical animal models and clinical outcome has alarmed us to search for a new strategy in the treatment of Alzheimer's disease (AD). Interlink between Pregnane X Receptor (PXR) and P-glycoprotein (Pgp) at the blood brain barrier (BBB) has raised hope toward a new disease modifying therapy in AD. Pgp is a major efflux transporter for beta amyloid (Aβ) at human BBB.

Predicting drug metabolism by CYP1A1, CYP1A2, and CYP1B1: insights from MetaSite, molecular docking and quantum chemical calculations.

Recently, CYP1 enzymes are documented for selective metabolism of anticancer leads in cancer prevention and/or progression. Elucidation of specificity of substrates/inhibitors of CYP1 isoforms plays a vital role in design of more selective and potent anticancer leads. However, an area of concern is the broad range of substrate specificities and planar nature of substrates with limited dataset which makes it difficult to predict their site of metabolism (SOM) accurately.

Human pregnane X receptor: a novel target for anticancer drug development.

Multidrug resistance (MDR), a significant barrier to effective pharmacokinetics and pharmacodynamics of anticancer drugs, is mainly due to the induction potential of anticancer drugs for drug metabolizing enzymes (DMEs) and efflux transporters through nuclear receptors. Human Pregnane X Receptor (hPXR) is master transcription factor for cytochrome P450 3A4 (CYP3A4) and multidrug resistance protein 1 (MDR1). The hPXR is capable of being activated by structurally diverse ligands.