Understanding the Oral Absorption of Irbesartan Using Biorelevant Dissolution Testing and PBPK Modeling.

Poorly soluble weak bases form a significant proportion of the drugs available in the market thereby making it imperative to understand their absorption behavior. This work aims to mechanistically understand the oral absorption behavior for a weakly basic drug, Irbesartan (IRB), by investigating its pH dependent solubility, supersaturation, and precipitation behavior. Simulations performed using the equilibrium solubility could not accurately predict oral absorption.

Assessment of Biopharmaceutical Performance of Supersaturating Formulations of Carbamazepine in Rats Using Physiologically Based Pharmacokinetic Modeling.

There is an overgrowing emphasis on supersaturating drug delivery systems (SDDS) with increase in number of poorly water-soluble compounds. However, biopharmaceutical performance from these formulations is limited by phase transformation to stable crystalline form due to their high-energy physical form. In the present study, in vitro kinetic solubility in water and dissolution in biorelevant medium integrated with in silico physiologically based pharmacokinetic (PBPK) modeling was used to predict biopharmaceutical performance of SDDS of poorly water-soluble compound, carbamazepine (CBZ).

LINCRNA00273 promotes cancer metastasis and its G-Quadruplex promoter can serve as a novel target to inhibit cancer invasiveness.

Discovery of anti-metastatic drugs is of immense clinical significance as metastasis is responsible for 90% of all cancer deaths. Here we report the inhibitory effect of a bis schiff base (M2) on cancer cell migration and invasion and . M2 has shown good solubility and permeability across the intestinal cell wall and hence can be classified as BCS (Biopharmaceutical classification system) class I.

Leucine-684: A conserved residue of an AMP-acetyl CoA synthetase (AceCS) from Leishmania donovani is involved in substrate recognition, catalysis and acetylation.

AMP-acetyl CoA synthetase (AMP-AceCS) is a key enzyme which catalyzes the activation of acetate to acetyl CoA, an important intermediate at the cross roads of various anabolic and catabolic pathways. Multiple sequence alignment of Leishmania donovani AceCS with other organisms revealed the presence of a highly conserved leucine residue at 684 position which is known to be crucial for acetylation by protein acetyl transferases in other organisms. In an attempt to understand the role of leucine residue at 684 position in L.

IPAT: a freely accessible software tool for analyzing multiple patent documents with inbuilt landscape visualizer.

Intelligent Patent Analysis Tool (IPAT) is an online data retrieval tool, operated based on text mining algorithm to extract specific patent information in a predetermined pattern into an Excel sheet. The software is designed and developed to retrieve and analyze technology information from multiple patent documents and generate various patent landscape graphs and charts. The software is C# coded in visual studio 2010, which extracts the publicly available patent information from the web pages like Google Patent and simultaneously study the various technology trends based on user-defined parameters.

2'-Hydroxy flavanone derivatives as an inhibitors of pro-inflammatory mediators: Experimental and molecular docking studies.

2'-Hydroxy flavanone (1) was previously isolated from Mimosa pudica (L.) whole plant and was found to exhibit anti-inflammatory effects in vitro. There are also reports on anti-inflammatory properties of compounds bearing flavanone/chromone nucleus.

Characterization of degradation products of ivabradine by LC-HR-MS/MS: a typical case of exhibition of different degradation behaviour in HCl and H2SO4 acid hydrolysis.

A validated stability-indicating HPLC method was established, and comprehensive stress testing of ivabradine, a cardiotonic drug, was carried out as per ICH guidelines. Ivabradine was subjected to acidic, basic and neutral hydrolysis, oxidation, photolysis and thermal stress conditions, and the resulting degradation products were investigated by LC-PDA and LC-HR-MS/MS. The drug was found to degrade in acid and base hydrolysis.

Synthesis, biological evaluation and 3D QSAR study of 2,4-disubstituted quinolines as anti-tuberculosis agents.

The synthesis and anti-tuberculosis activity for three series of 2,4-disubstituted quinolines is reported. The synthesized compounds were evaluated for activity against M. tuberculosis H37Rv strain; most promising compounds from the series exhibited MIC99 values ranged between 3.

Structure based virtual screening to identify selective phosphodiesterase 4B inhibitors.

Phosphodiesterase 4 (PDE4), is a hydrolytic enzyme, is proposed as a promising target in asthma and chronic obstructive pulmonary disease. PDE4B selective inhibitors are desirable to reduce the dose limiting adverse effect associated with non-selective PDE4B inhibitors. To achieve this goal, ligand based pharmacophore modeling and molecular docking approach is employed.

Biological evaluation and structural insights for design of subtype-selective peroxisome proliferator activated receptor-α (PPAR-α) agonists.

Peroxisome proliferator activated receptors-α (PPAR-α) control the expression of several genes involved in diseases like diabetes, hyperlipidaemia, and inflammatory disorders. Herein, we report the biological evaluation of recently identified hits from pharmacophore based virtual screening. The most potent hits, ZINC17167211, ZINC06472206 and ZINC08438472 showed EC50 values of 0.

Oleanolic acid analogs as NO, TNF-α and IL-1β inhibitors: synthesis, biological evaluation and docking studies.

A series of oleanolic acid analogs, characterized by structural modifications at position C-3 and C-28 of oleanane skeleton were synthesized and assessed for antiinflammatory potential towards lipopolysaccharide (LPS) induced nitric oxide (NO) production in macrophages. Results revealed that all the synthesized analogs of oleanolic acid inhibit NO production with an IC50 of 2.66-41.

Synthesis, biological evaluation and 3D-QSAR study of hydrazide, semicarbazide and thiosemicarbazide derivatives of 4-(adamantan-1-yl)quinoline as anti-tuberculosis agents.

We report synthesis, anti-tuberculosis activity and 3D-QSAR study of forty nine hydrazide, semicarbazide and thiosemicarbazide derivatives of 4-(adamantan-1-yl)quinoline. The most potent compounds upon evaluation for anti-tuberculosis activity exhibited MIC99 of 3.125 μg/mL against Mycobacterium tuberculosis H37Rv strain.

Effect of different "states" of sorbed water on amorphous celecoxib.

Glass transition temperature (Tg) of an amorphous drug is a vital physical phenomenon that influences its visco-elastic properties, physical, and chemical stability. Water acts as a plasticizer for amorphous drugs thus increasing their recrystallization kinetics. This reduces the solubility advantage of an amorphous drug.

Neuroprotective Potential of Peroxisome Proliferator Activated Receptor- α Agonist in Cognitive Impairment in Parkinson's Disease: Behavioral, Biochemical, and PBPK Profile.

Parkinson's disease (PD) is a common neurodegenerative disorder affecting 1% of the population by the age of 65 years and 4-5% of the population by the age of 85 years. PD affects functional capabilities of the patient by producing motor symptoms and nonmotor symptoms. Apart from this, it is also associated with a higher risk of cognitive impairment that may lead to memory loss, confusion, and decreased attention span.

A PPAR-β/δ agonist is neuroprotective and decreases cognitive impairment in a rodent model of Parkinson's disease.

Parkinson's disease (PD) is associated with higher risk of cognitive impairment that may lead to memory loss, confusion, and decreased attention span. In this study, we have investigated the effect of GW0742, a PPAR-β/δ agonist in rat model of cognitive impairment associated with PD. Bilateral intranigral administration of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) (100 µg/1 µl/side) produced significant cognitive dysfunctions.

Identification of p38α MAP kinase inhibitors by pharmacophore based virtual screening.

The p38α mitogen-activated protein (MAP) kinase plays a vital role in treating many inflammatory diseases. In the present study, a combined ligand and structure based pharmacophore model was developed to identify potential DFG-in selective p38 MAP kinase inhibitors. Conformations of co-crystallised inhibitors were used in the development and validation of ligand and structure based pharmacophore modeling approached.

p38 Mitogen-activated protein kinase inhibitors: a review on pharmacophore mapping and QSAR studies.

p38 mitogen-activated protein (MAP) kinases are the serine/threonine protein kinases, which play a vital role in cellular responses to external stress signals. p38 MAP kinase inhibitors have shown anti-inflammatory effects in the preclinical disease models, primarily through inhibition of the expression of inflammatory mediators. A number of structurally diverse p38 MAP kinase inhibitors have been developed as potential anti-inflammatory agents.

Oral delivery of anticancer drugs: challenges and opportunities.

The present report focuses on the various aspects of oral delivery of anticancer drugs. The significance of oral delivery in cancer therapeutics has been highlighted which principally includes improvement in quality of life of patients and reduced health care costs. Subsequently, the challenges incurred in the oral delivery of anticancer agents have been especially emphasized.

Identification of dual Acetyl-CoA carboxylases 1 and 2 inhibitors by pharmacophore based virtual screening and molecular docking approach.

Acetyl-CoA carboxylase (ACC) is a crucial metabolic enzyme that plays a vital role in obesity-induced type 2 diabetes and fatty acid metabolism. To identify dual inhibitors of Acetyl-CoA carboxylase1 and Acetyl-CoA carboxylase2, a pharmacophore modelling approach has been employed. The best HypoGen pharmacophore model for ACC2 inhibitors (Hypo1_ACC2) consists of one hydrogen bond acceptor, one hydrophobic aliphatic and one hydrophobic aromatic feature, whereas the best pharmacophore (Hypo1_ACC1) for ACC1 consists of one additional hydrogen-bond donor (HBD) features.

3D-QSAR and molecular docking analysis of biphenyl amide derivatives as p38α mitogen-activated protein kinase inhibitors.

The p38α mitogen-activated protein (MAP) kinase plays a vital role in treating many inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, Crohn's disease and psoriasis. Herein, we have performed 3D-QSAR and molecular docking analysis on a novel series of biphenyl amides to design potent p38 MAP kinase inhibitors. This study correlates the p38 MAP kinase inhibitory activities of 80 biphenyl amide derivatives to several stereochemical parameters representing steric, electrostatic, hydrophobic, hydrogen bond donor and acceptor fields.