Elucidation of the Role of TRPV1, VEGF-A, TXA2, Redox Homeostasis, and Inflammatory Cascades in Protection against Cold Injuries by Herbosomal-Loaded PEG-Poloxamer Topical Formulation.

High-altitude regions, cold deserts, permafrost regions, and the polar region have some of the severest cold conditions on earth and pose immense perils of cold injuries to exposed individuals. Accidental and unintended exposures to severe cold, either unintentionally or due to occupational risks, can greatly increase the risk of serious conditions including hypothermia, trench foot, and cold injuries like frostbite. Cold-induced vasoconstriction and intracellular/intravascular ice crystal formation lead to hypoxic conditions at the cellular level.

Enhancing oral bioavailability of Ca-DTPA by self double emulsifying drug delivery system (SDEDDS).

Objective: BCS class III drug (highly soluble, poorly permeable) possesses low oral bioavailability. The research work highlights the utility of self-double emulsifying drug delivery system (SDEDDS) which are stable isotropic mixture of w/o primary emulsion and hydrophilic surfactants for improving oral bioavailability of Ca-DTPA (Calcium diethylenetriamine pentaacetate). Upon oral administration, SDEDDS rapidly emulsifies into w/o/w double emulsions in the aqueous gastrointestinal environment, with hydrophilic drugs entrapped inside oil reservoirs.

Crystallographic mining driven computer-guided approach to identify the ASK1 inhibitor likely to perturb the catalytic region.

The pathological levels of reactive oxygen species (ROS) and oxidative stress has been recognized as a critical driver for inflammatory disorders. Apoptosis signal-regulating kinase 1 (ASK1) has been reported to be activated by intracellular ROS and its inhibition leads to a down regulation of p38-and JNK-dependent signaling. ASK1 inhibitors are reported to have the potential to treat clinically important inflammatory pathologies including liver, pulmonary and renal disorders.

Deciphering the Structural Determinants Critical in Attaining the FXR Partial Agonism.

Elucidation of structural determinants is pivotal for structure-based drug discovery. The Farnesoid X receptor (FXR) is a proven target for NASH; however, its full agonism causes certain clinical complications. Therefore, partial agonism (PA) appears as a viable alternative for improved therapeutics.

Design and optimization of a novel herbosomal-loaded PEG-poloxamer topical formulation for the treatment of cold injuries: a quality-by-design approach.

The spectrum of cold injuries ranges from frostnip, chilblains to severe frostbite. Cold injuries occur upon prolonged exposure to freezing temperature and are pathologically a combination of ice crystal formation in the tissue resulting in inflammation, thrombosis and ischemia in the extremities, often necessitating limb amputation in extreme cases due to tissue necrosis. Severe forms of frostbite are a cause of major concern to patients as well as the treating physician.

Conformational Characterization of the Co-Activator Binding Site Revealed the Mechanism to Achieve the Bioactive State of FXR.

FXR bioactive states are responsible for the regulation of metabolic pathways, which are modulated by agonists and co-activators. The synergy between agonist binding and 'co-activator' recruitment is highly conformationally driven. The characterization of conformational dynamics is essential for mechanistic and therapeutic understanding.

In-vitro Evaluation of Isatin Derivatives as Potent Anti-Breast Cancer Agents against MCF-7, MDA MB 231, MDA-MB 435 and MDA-MB 468 Breast Cancers Cell Lines: A Review.

Introduction: Breast cancer (BC) is one of the most frequent malignancies and the most common reasons for impermanence in women. The backbone of therapy for BC is principally chemotherapy, but its non-specific nature to differentiate between normal cells and cancer cells and severe side effects are the main barriers in its use. So, there is an intense requirement to enlarge more efficacious, more specific and safer anti-BC agents.

Application of Methods in the Design of Drugs for Neurodegenerative Diseases.

Neurodegenerative diseases are complex disorders that cause neuron loss, brain aging and ultimately lead to death. These diseases are difficult to treat because of the complex nature of the nervous system, and the available medicines are unable to heal them effectively. This fact implies the need for novel therapeutics to be designed that are ready to stop or a minimum of retard the neurodegeneration process.

pH-dependent Release Matrix Oral Formulation of Prussian Blue to Improve its Efficacy as an Internal Decorporation Agent.

Background: Prussian Blue (PB) is available as conventional release dosage form "Radiogardase" with effective daily dose of 3-10 g (very high). The target site is the duodenum, where it inhibits the enterohepatic circulation of Cs & Tl ions, enhancing their fecal excretion.

Objective: To enhance efficacy, target release, reduce the dose and side effects, oral pH-dependent matrix formulation of PB based on in-situ gelation of sodium alginate along with calcium salts was formulated and evaluated.

Advances in Synthesis, Derivatization and Bioactivity of Isatin: A Review.

Background: Isatin (IST) is a crucial pharmacologically active compound, chemically known as indole- 1H-2,3-dione. Development of different IST based analogues acquired significant awareness because of its pronounced therapeutic importance such as analgesic, anticancer, anti-inflammatory, antitubercular, antimicrobial, antifungal, antiviral (effective against SARS coronavirus 3C protease) and many other activities, and represents an important class of heterocyclic compounds that can be used as a precursor for the synthesis of many useful drugs.

Objective: Previously, many articles were reported on IST synthesis and its different pharmacological activities but herein, we mentioned 59 different synthesis schemes of several IST derivatives/hybrids derived from the substitution of the nitrogen, aromatic ring, the second and third position of IST along with most potent molecule among each of synthesized libraries with their structural activity relationship (SAR).

Synthesis, ADME, docking studies and in vivo anti-hyperglycaemic potential estimation of novel Schiff base derivatives from octadec-9-enoic acid.

A new series of octadec-9-enoic acid schiff base entities (S1-S30) were designed and synthesized targeting peroxisome proliferator activated receptor-gamma for agonist action. Molinspiration software (online) was used to estimate drug like molecular properties of the metabolites. Docking disquisition on co-crystallized protein of PPAR-γ (PDB ID 1FM9) was carried out which showed S21, S10 and S7 as best situated in the vital sites of receptor having docking scores -9.

Novel hybrids of benzothiazole-1,3,4-oxadiazole-4-thiazolidinone: Synthesis, in silico ADME study, molecular docking and in vivo anti-diabetic assessment.

A series of new benzothiazole-1,3,4-oxadiazole-4-thiazolidinone hybrid analogs (Tz1-Tz28) were synthesized in search of potential anti-diabetic agents. Molecular docking study was conducted with binding pocket of peroxisome proliferator activated receptor-gamma to elucidate the binding interactions of newly synthesized targets. Seven selected compounds with best docking scores were further screened for in vivo anti-hyperglycemic efficacy by oral glucose tolerance test in non-diabetic rats and on streptozotocin induced diabetic rat models.

Synthesis, biological evaluation and docking study of N-(2-(3,4,5-trimethoxybenzyl)benzoxazole-5-yl) benzamide derivatives as selective COX-2 inhibitor and anti-inflammatory agents.

A series of N-(2-(3,4,5-trimethoxybenzyl)-benzoxazole-5-yl)benzamide derivatives (3a-3n) was synthesized and evaluated for its in vitro inhibitory activity against COX-1 and COX-2. The compounds with considerable in vitro activity (IC < 1 µM), were evaluated in vivo for their anti-inflammatory and ulcerogenic potential. Out of the fourteen newly synthesized compounds; 3b, 3d, 3e, 3h, 3l and 3m were found to be most potent COX-2 inhibitors in in vitro enzymatic assay with IC in the range of 0.

Synthesis, molecular docking, and pharmacological evaluation of N-(2-(3,5-dimethoxyphenyl)benzoxazole-5-yl)benzamide derivatives as selective COX-2 inhibitors and anti-inflammatory agents.

A series of N-(2-(3,5-dimethoxyphenyl)benzoxazole-5-yl)benzamide derivatives (3am) was synthesized and evaluated for their in vitro inhibitory activity against COX-1 and COX-2. The compounds with considerable in vitro activity (IC  < 1 μM) were evaluated in vivo for their anti-inflammatory potential by the carrageenan-induced rat paw edema method. Out of 13 newly synthesized compounds, 3a, 3b, 3d, 3g, 3j, and 3k were found to be the most potent COX-2 inhibitors in the in vitro enzymatic assay, with IC values in the range of 0.

Designing novel inhibitors against falcipain-2 of Plasmodium falciparum.

Coumarin containing pyrazoline derivatives have been synthesized and tested as inhibitors of in vitro development of a chloroquine-sensitive (MRC-02) and chloroquine-resistant (RKL-2) strain of Plasmodium falciparum and in vivo Plasmodium berghei malaria. Docking study was also done on cysteine protease falcipain-2 which showed that the binding pose of C-14 molecule and epoxysuccinate, inhibitor of falcipain-2, binds in the similar pattern. The most active antimalarial compound was 3-(1-benzoyl-5-(4-flurophenyl)-4,5-dihydro-1H-pyrazol-3yl)-7-(diethyamino)-2H-chromen-2-one C-14, with an IC of 4.

Synthesis, Cyclooxygenase-2 Inhibition, Anti-inflammatory Evaluation and Docking Study of Substituted-N-(3,4,5-trimethoxyphenyl)-benzo[d]oxazole Derivatives.

Background: Non-steroidal anti-inflammatory drugs are widely used for many years, but the chronic use of NSAID's leads to gastric side effects, ulceration and kidney problems. These side effects are due to non-selective inhibition of COX-2 along with COX-1. Therefore, it is imperative to develop novel and selective COX-2 inhibitors.

Synthesis, biological evaluation and docking study of a new series of di-substituted benzoxazole derivatives as selective COX-2 inhibitors and anti-inflammatory agents.

A new series of substituted-N-(3,4-dimethoxyphenyl)-benzoxazole derivatives 13a-13p was synthesized and evaluated in vitro for their COX (I and II) inhibitory activity, in vivo anti-inflammatory and ulcerogenic potential. Compounds 13d, 13h, 13k, 13l and 13n exhibited significant COX-2 inhibitory activity and selectivity towards COX-2 over COX-1. These selected compounds were screened for their in vivo anti-inflammatory activity by carrageenan induced rat paw edema method.

Preparation, Characterization, and Pharmacoscintigraphy Evaluation of an Intestinal Release Delivery System of Prussian Blue for Decorporation of Cesium and Thallium.

Background: Prussian blue (PB, ferric hexacyanoferrate) is approved by US-FDA for internal decorporation of Cesium-137 (Cs) and Thallium-201 (Tl).

Aim: Since PB is a costly drug, pH-dependent oral delivery system of PB was developed using calcium alginate matrix system.

Methods: Alginate (Alg) beads containing PB were optimized by gelation of sodium alginate with calcium ions and effect of varying polymer concentration on encapsulation efficiency and release profile was investigated.

Synthesis, molecular modelling studies and ADME prediction of benzothiazole clubbed oxadiazole-Mannich bases, and evaluation of their anti-diabetic activity through in vivo model.

A small library of new benzothiazole clubbed oxadiazole-Mannich bases (M-1 to M-22) were synthesized and characterized by IR, NMR, Mass and Elemental analysis results. Molecular docking studies were done to assess the binding mode and interactions of synthesized hits at binding site of receptor Peroxisome proliferator-activated receptor, PPAR-γ or PPARG (PDB 1FM9). Among the synthesized compounds, nine compounds were selected on the basis of docking score and evaluated for their in vivo anti-diabetic activity using Oral Glucose Tolerance Test (OGTT) in normal rats followed by Streptozotocin (STZ) - induced diabetes.

Ex-vivo complexation, skin permeation, interaction and cytodermal toxicity studies of p-tertbutylcalix[4]arene nanoemulsion for radiation decontamination.

Aims: p-tertbutylcalix[4]arene loaded nanoemulsion has been designed, characterized and evaluated for skin decontamination of radionuclides of interest in nuclear and radiological emergencies. Further, nanoemulsion was evaluated for Ex-vivo complexation, skin permeation, interaction and cytodermal toxicity.

Materials And Methods: Ex-vivo skin complexation studies were conducted using High-resolution sector field inductively coupled plasma mass spectroscopy (HR-SF-ICPMS).

Design and evaluation of acrylate polymeric carriers for fabrication of pH-sensitive microparticles.

Colon-targeted microparticles loaded with a model anti-inflammatory drug were fabricated using especially designed acrylic acid-butyl methacrylate copolymers. Microparticles were prepared by oil-in-oil solvent evaporation method using Span 80 as emulsifier. Microparticles were found to be spherical in shape, hemocompatible and anionic with zeta potential of -27.

Imidazole Derivatives as Potential Therapeutic Agents.

Background: The imidazole nucleus is inimitable and ubiquitous and it is very well known to play an important role in living organisms. Imidazole derivatives are under intensive scientific exploration due to their diverse and significant pharmacological activities.

Methods: The present paper is an attempt to discuss chemistry, synthetic aspects including click chemistry procedures of imidazoles through systematic literature survey.

Medicinal significance of benzothiazole scaffold: an insight view.

Heterocycles bearing nitrogen, sulphur and thiazole moieties constitute the core structure of a number of biologically interesting compounds. Benzothiazole, a group of xenobiotic compounds containing a benzene ring fused with a thiazole ring, are used worldwide for a variety of therapeutic applications. Benzothiazole and their heterocyclic derivatives represent an important class of compounds possessing a wide spectrum of biological activities.