A Combined Approach of Pharmacophore Modeling, QSAR Study, Molecular Docking and In silico ADME/Tox Prediction of 4-Arylthio & 4-Aryloxy-3- Iodopyridine-2(1H)-one Analogs to Identify Potential Reverse Transcriptase Inhibitor: Anti-HIV Agents.

Background: Reverse transcriptase is an important therapeutic target to treat AIDS caused by the Human Immunodeficiency Virus (HIV). Despite many effective anti-HIV drugs, reverse transcriptase (RT) inhibitors remain the cornerstone of the drug regimen to treat AIDS. In the present work, we have expedited the use of different computational modules and presented an easy, costeffective, and high throughput screening method to identify potential reverse transcriptase inhibitors.

Identification of Antimycobacterial Agent Using In Silico Virtual Screening, ADME Prediction, Docking, and Molecular Dynamics Simulations Approach.

Background: The widespread hazardous issue of antibiotics resistance can be overcome by the development of target based potent antibacterial agents. Filamentous temperature-sensitive mutant Z (FtsZ), a simpler structural prokaryotic homolog of eukaryotic cytoskeletal tubulin, was considered as a competent target in antibacterial drug discovery.

Objective: The purpose of the present work is to evaluate the antitubercular activity of virtual hits by funnel-shaped filtering with glide docking, followed by MM-GBSA binding energy and molecular dynamics simulation.

Modified apple polysaccharide capped gold nanoparticles for oral delivery of insulin.

The study entailed formulation of gold nanoparticles (AuNPs) upon reduction of chloroauric acid by modified apple polysaccharide (MAP). AuNPs were conjugated with insulin (INS) for its oral delivery to treat type 1 diabetes mellitus (DM). The size of MAP conjugated AuNPs loaded with INS was 124 ± 8.

Computer-aided identification of lead compounds as Staphylococcal epidermidis FtsZ inhibitors using molecular docking, virtual screening, DFT analysis, and molecular dynamic simulation.

In an effort to face the multiple drug-resistant bacteria, various approaches have been discovered to design potent compounds and search new targets through computational design tools. With an aim to identify selective inhibitors against filamentous temperature-sensitive mutant Z (FtsZ), a library of Phase database compounds have been virtually screened. High-throughput virtual screening of compounds against Staphylococcal epidermidis FtsZ protein (4M8I) was performed using three sequential docking modes like high-throughput virtual screening, Glide standard precision, followed by Glide extra precision.

A combination of resveratrol and 3,3'-diindolylmethane, a potent radioprotector.

Purpose: Exposure to ionizing radiation causes damage to the genomic integrity and stability of the cell. Though a large number of molecules have been studied for their radioprotective capability, no single agent is available today that meets all the requirements of a good radiprotector. In this study, we have investigated a combination of Resveratrol (RSV) and 3,3'-Diindolyl methane (DIM) for its efficacy for radioprotection.

A Novel Three-pronged Approach for Colon Delivery of Sulfasalazine: Concomitant Use of pH- Responsive, Microbially Triggered Polymers and Liquisolid Technology.

Objective: A major challenge in targeting orally administered drugs to colon is their passage through the long gastrointestinal path comprising highly variant conditions in terms of pH, viscosity, gut motility and microbial flora. Approaches to pH controlled release and microbially triggered release have proved to be successful in achieving colon targeting only to a partial extent.

Methods: In an attempt to improve targeting, both these approaches have been combined together with the approach of liquisolid technology which, hitherto, remains unexplored for colon targeting.

Prediction of Human Pharmacokinetics of Ulixertinib, a Novel ERK1/2 Inhibitor from Mice, Rats, and Dogs Pharmacokinetics.

Background And Objectives: Ulixertinib (BVD-523) is a novel and selective reversible inhibitor of ERK1/ERK2. The primary objectives of the study were to evaluate the pharmacokinetics of ulixertinib in mice, rats, and dogs followed by prediction of human pharmacokinetic profile by allometric equations with/without correction factors.

Methods: Oral and intravenous pharmacokinetic profiles of ulixertinib were generated in mice, rats, and dogs.

Impact of various solid carriers and spray drying on pre/post compression properties of solid SNEDDS loaded with glimepiride: in vitro-ex vivo evaluation and cytotoxicity assessment.

Development of self-nanoemulsifying drug delivery systems (SNEDDS) of glimepiride is reported with the aim to achieve its oral delivery. Lauroglycol FCC, Tween-80, and ethanol were used as oil, surfactant, and co-surfactant, respectively as independent variables. The optimized composition of SNEDDS formulation (F1) was 10% v/v Lauroglycol FCC, 45% v/v Tween 80, 45% v/v ethanol, and 0.

Novel biorelevant dissolution medium as a prognostic tool for polysaccharide-based colon-targeted drug delivery system.

To overcome the limitations of the conventionally used methods for evaluation of orally administered colon-targeted delivery systems, a novel dissolution method using probiotics has been recently reported. In the present study, universal suitability of this medium composed of five different probiotics is established. Different delivery systems - mini tablets, liquisolid compacts, and microspheres coated with different polysaccharides - were prepared and subjected to sequential dissolution testing in medium with and without microbiota.

Pharmacophore generation, atom-based 3D-QSAR, molecular docking and molecular dynamics simulation studies on benzamide analogues as FtsZ inhibitors.

FtsZ is an appealing target for the design of antimicrobial agent that can be used to defeat the multidrug-resistant bacterial pathogens. Pharmacophore modelling, molecular docking and molecular dynamics (MD) simulation studies were performed on a series of three-substituted benzamide derivatives. In the present study a five-featured pharmacophore model with one hydrogen bond acceptors, one hydrogen bond donors, one hydrophobic and two aromatic rings was developed using 97 molecules having MIC values ranging from .

Extra precision docking, free energy calculation and molecular dynamics studies on glutamic acid derivatives as MurD inhibitors.

The binding modes of well known MurD inhibitors have been studied using molecular docking and molecular dynamics (MD) simulations. The docking results of inhibitors 1-30 revealed similar mode of interaction with Escherichia coli-MurD. Further, residues Thr36, Arg37, His183, Lys319, Lys348, Thr321, Ser415 and Phe422 are found to be important for inhibitors and E.

Simultaneous blockade of NMDA receptors and PARP-1 activity synergistically alleviate immunoexcitotoxicity and bioenergetics in 3-nitropropionic acid intoxicated mice: Evidences from memantine and 3-aminobenzamide interventions.

Interlink between excitotoxicity and cellular bioenergetics depletion is implicated as one of the central deteriorative pathways in many neurodegenerative diseases including Huntington's disease (HD). Chronic administration of 3-nitropropionic acid (3-NP) depletes ATP and NAD and increases TNFα, IL-6 and glutamate content resulting in "immunoexcitotoxicity". Present study was designed to determine whether the combination of memantine (MN) and 3-aminobenzamide (3-AB), PARP inhibitor, can ameliorate immunoexcitotoxicity and improve bioenergetics in a better manner than individual administration against 3-NP intoxication in mice.

Stable Co-crystals of Glipizide with Enhanced Dissolution Profiles: Preparation and Characterization.

Present study deciphers preparation of co-crystals of lipophilic glipizide by using four different acids, oxalic, malonic, stearic, and benzoic acids, in order to achieve enhanced solubility and dissolution along with stability. All co-crystals were prepared by dissolving drug and individual acids in the ratio of 1:0.5 in acetonitrile at 60-70°C for 15 min, followed by cooling at room temperature for 24 h.

Improved anti-tumor activity of oxaliplatin by encapsulating in anti-DR5 targeted gold nanoparticles.

Oxaliplatin is one of the chemotherapeutic agents in the first line therapy for treatment of colorectal cancer. But, limitations of chemotherapy affects the clinical applicability of oxaliplatin depriving its activity at targeted site attributed to the lack of site specificity. This limitation paves the way for undesirable toxic effects to healthy cells resulting in sub-standard drug amount at the tumors obliging for increased dose.

Antioxidant Studies on Ethanol Extracts from Two Selected Genera of Indian Lamiaceae.

The present work is targeted to evaluate antioxidant activity of ethanol extracts from the leaves of Plectranthus mollis and Salvia officinalis belonging to family Lamiaceae using nitric oxide scavenging, hydrogen peroxide scavenging, ferric reducing antioxidant power assay and lipid peroxidation methods. The results of the study indicate that the leaf extracts of both the plants possess in vitro antioxidant activity. The higher amount of flavanoids and phenolic compounds may correspond to their greater antioxidant activity.

Oxaliplatin immunohybrid nanoparticles in vitro synergistic suppression evaluation in treatment of colorectal cancer.

In the present study, we have investigated the enhanced synergistic and apoptotic activity of immunohybrid nanoparticles encapsulating oxaliplatin and covalently conjugated with TRAIL (Apo-2L/CD-253). Time-dependent cytotoxicity activity of nanoparticles was determined by MTT assay in HT-29 cells. Nuclear morphological changes and assessment of apoptotic ratio was analyzed by DAPI (4'6-diamidino-2-phenylindole) staining and annexin-propidium iodide (PI) assay.

Effects of Gymnema sylvestre extract on the pharmacokinetics and pharmacodynamics of glimepiride in streptozotocin induced diabetic rats.

Gymnema sylvestre, important Indian traditional herbal medicine has been used for diabetes from several years and marketed as single or multi-herb formulations globally. People are consuming G. sylvestre along with conventional hypoglycemic drugs.

5-Fluorouracil enteric-coated nanoparticles for improved apoptotic activity and therapeutic index in treating colorectal cancer.

5-Fluorouracil (5-FU) is one among the anti-cancer agents in FOLFORINOX treatment along with oxaliplatin and irinotecan for the treatment of colorectal cancer. Despite its potential activity on the tumor cells, it lacks site specificity partly attributed by its biodistribution to healthy cells resulting in toxic effects to healthy cells. Therefore, we have formulated 5-fluorouracil enteric-coated nanoparticles (5-FUEC) to localize the drug in the colon area that enables its prolonged presence in target area in a sustained manner.

A combination of pharmacophore modeling, atom-based 3D-QSAR, molecular docking and molecular dynamics simulation studies on PDE4 enzyme inhibitors.

Phosphodiesterases 4 enzyme is an attractive target for the design of anti-inflammatory and bronchodilator agents. In the present study, pharmacophore and atom-based 3D-QSAR studies were carried out for pyrazolopyridine and quinoline derivatives using Schrödinger suite 2014-3. A four-point pharmacophore model was developed using 74 molecules having pIC50 ranging from 10.

Pharmacophore modeling, 3D-QSAR, and docking study of pyrozolo[1,5-a]pyridine/4,4-dimethylpyrazolone analogues as PDE4 selective inhibitors.

Phosphodiesterases 4 enzyme is an attractive target for the design of anti-inflammatory and bronchodilator agents. In the present study pharmacophore and atom based 3D-QSAR studies were carried out for pyrozolo[1,5-a]pyridine/4,4-dimethylpyrazolone analogues. A five point pharmacophore model was developed using 52 molecules having pIC50 values ranging from 9.

Effect of co-administration of probiotics with polysaccharide based colon targeted delivery systems to optimize site specific drug release.

Significant clinical success of colon targeted dosage forms has been limited by their inappropriate release profile at the target site. Their failure to release the drug completely in the colon may be attributed to changes in the colonic milieu because of pathological state, drug effect and psychological stress accompanying the diseased state or, a combination of these. Alteration in normal colonic pH and bacterial picture leads to incomplete release of drug from the designed delivery system.

Oxaliplatin immuno hybrid nanoparticles for active targeting: an approach for enhanced apoptotic activity and drug delivery to colorectal tumors.

Tumor necrosis factor related apoptosis inducing ligand (TRAIL) proved to be a promising new target for colorectal cancer treatment. Elevated expression of TRAIL protein in tumor cells distinguishes it from healthy cells, thereby delivering the drug at the specific site. Here, we formulated oxaliplatin immunohybrid nanoparticles (OIHNPs) to deliver oxaliplatin and anti-TRAIL for colorectal cancer treatment in xenograft tumor models.

Isolation of methyl gamma linolenate from Spirulina platensis using flash chromatography and its apoptosis inducing effect.

Background: Isolation of methyl gamma linolenate from Spirulina platensis using flash chromatography and its apoptosis inducing effect against human lung carcinoma A- 549 cell lines.

Methods: Gamma linolenic acid is an important omega-6 polyunsaturated fatty acid (PUFA) of medicinal interest was isolated from microalgae Spirulina platensis using flash chromatography system (Isolera system) as its methyl ester. The isolated methyl gamma linolenate was characterized by IR, (1)H NMR, (13)C NMR and mass spectral analysis and the data were consistent with the structure.

Bioavailability study of calcium sandoz-250 by atomic absorption spectroscopy in albino rats.

Background: Calcium sandoz-250 is an Ayurvedic calcium supplement, containing Khatika Churna. Bioavailability study of the formulation is essential for estimation of peak plasma concentration (C max), time to C max and rate of absorption.

Aim: To evaluate the absorption parameters of calcium sandoz-250 in albino rats by atomic absorption spectroscopic (AAS) method.