Imperatorin, a natural furanocoumarin alleviates chronic neuropathic pain by targeting GABAergic tone in an animal model of spinal cord injury.

Chronic neuropathic pain (CNP) caused by spinal cord injury (SCI) has long-term implications, that result in functional deficit. In this study, we explored imperatorin, a natural furanocoumarin isolated from the dried pulp of L. Imperatorin (10 mg/kg, i.

In-silico and In-vitro Investigation of Flavonoids and Alkaloids from Artocarpus heterophyllus, Tinospora cordifolia, and Glycosmis pentaphylla as Potential NF-κB Inhibitors in Oral Cancer.

Oral cancer is a global health concern, particularly because of its aggressive tissue invasion and metastases, holding 16 position on occurrence among all carcinoma worldwide. The aberrated transcription factor NF-κB1 influences development and spread of oral cancer, making it a potential therapeutic target. This study investigated the therapeutic potential of a few natural compounds from Artocarpus heterophyllus, Tinospora cordifolia, and Glycosmis pentaphylla in the treatment of oral cancer.

Isolation and characterization of bioactive alkaloids and GC-MS based identification of volatile oil metabolites from fruits of Glycosmis pentaphylla and evaluation of their cytotoxic activity.

Glycosmis pentaphylla, a member of the Rutaceae family, has been extensively studied for its pharmacological activities, focusing mainly on the cytotoxic properties of its roots and stems. Conversely, limited researched has been done in terms of the phytochemical composition of the fruits. The objective of this study is to isolate and identify the bioactive compounds found in the fruits of G.

Development of stability-indicating assay method and liquid chromatography-quadrupole-time-of-flight mass spectrometry-based structural characterization of the forced degradation products of alpelisib.

The US Food and Drug Administration and the European Medicines Agency approved alpelisib in 2019 for the treatment of metastatic breast cancer. A thorough literature review revealed that a stability-indicating analytical method (SIAM) is not available for the quantification of alpelisib and its degradation products (DPs). In this study, per the comprehensive stress study recommended by the International Council for Harmonisation (ICH), alpelisib was exposed to hydrolysis, oxidation, photolysis, and thermal stress.

A strategy for evaluation of isotopic enrichment and structural integrity of deuterium labelled compounds by using HR-MS and NMR.

Determining the purity of deuterium labelled compounds is important due to the increasing use of these compounds in mass spectrometry (MS) based quantitative analyses for targeting metabolic flux, reducing toxicity, confirming reaction mechanisms during synthesis, predicting enzyme mechanisms, and enhancing the efficacy of drugs, in quantitative proteomics, and also as internal standards. In the present study, a strategy using liquid chromatography electrospray ionization high resolution mass spectrometry (LC-ESI-HR-MS) and nuclear magnetic resonance (NMR) spectroscopy was proposed to determine the isotopic enrichment and structural integrity of deuterium labelled compounds. The proposed strategy involves recording full scan MS, extracting and integrating isotopic ions, and calculating the isotopic enrichment of the desired labelled compounds.

RP-HPLC separation of interconvertible rotamers of a 5-tetrahydroisoquinolin-6-yl-pyridin-3-yl acetic acid derivative and confirmation by VT NMR and DFT study.

Due to emergence of drug resistance and drug tolerability, there is urgent need for discovery of new chemical entity for the treatment of HIV infection. As a part of in-house small molecule drug discovery program for HIV infection, sodium-2-(tert-butoxy)- 2-(5-(2-(2-chloro-6-methylbenzyl)- 1,2,3,4-tetrahydroisoquinolin-6-yl)- 4-(4,4-dimethylpiperidin-1-yl)- 2,6-dimethylpyridin-3-yl) acetate (SCMTDDA) was prepared as an intermediate for the synthesis of an API, designed as a HIV-1 integrase inhibitor. Initially, the final compound was isolated as a mixture of rotamers.

Herbal nanomedicines: Recent advancements, challenges, opportunities and regulatory overview.

Background: Herbal Nano Medicines (HNMs) are nano-sized medicine containing herbal drugs as extracts, enriched fractions or biomarker constituents. HNMs have certain advantages because of their increased bioavailability and reduced toxicities. There are very few literature reports that address the common challenges of herbal nanoformulations, such as selecting the type/class of nanoformulation for an extract or a phytochemical, selection and optimisation of preparation method and physicochemical parameters.

TGFβ Drives Metabolic Perturbations during Epithelial Mesenchymal Transition in Pancreatic Cancer: TGFβ Induced EMT in PDAC.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy wherein a majority of patients present metastatic disease at diagnosis. Although the role of epithelial to mesenchymal transition (EMT), mediated by transforming growth factor beta (TGFβ), in imparting an aggressive phenotype to PDAC is well documented, the underlying biochemical pathway perturbations driving this behaviour have not been elucidated. We used high-resolution mass spectrometry (HRMS) based molecular phenotyping approach in order to delineate metabolic changes concomitant to TGFβ-induced EMT in pancreatic cancer cells.

Traditional uses, phytochemistry, pharmacology, toxicology and formulation aspects of Glycosmis species: A systematic review.

The present article is a systematic and constructive review of the traditional medicinal uses, chemistry, pharmacology, toxicology, and formulation aspects of Glycosmis species. The genus Glycosmis comprise 51 accepted species broadly distributed in Australia, China, India, and South-East Asia. Traditionally, Glycosmis species are used in folk medicines to treat cancer, anaemia, rheumatism, fever, cough, liver-related problems, skin ailments, intestinal worm infections, wounds, and facial inflammation.

Synthesis and characterization of a series of N,N'-substituted urea derivatives by using electrospray ionization tandem mass spectrometry: Differentiation of positional isomers.

Rationale: Characterization of N,N'-substituted ureas was found to be challenging by nuclear magnetic resonance (NMR) spectroscopy, particularly N-di- and tri-alkylated ureas because of the absence of adjacent protons. In the present study, electrospray ionization tandem mass spectrometry has been used to differentiate positional isomeric pairs and to characterize a series of N,N'-substituted ureas, as these compounds have significant importance for drug discovery. Additionally, urea is an essential functionality in several bioactive compounds as well as a variety of clinically approved therapies.

Applications of 2, 2, 2 trifluoroethanol as a versatile co-solvent in supercritical fluid chromatography for purification of unstable boronate esters, enhancing throughput, reducing epimerization, and for additive free purifications.

Analysis and purification of boronic acid pinacol esters by RPLC is very challenging due to their degradation in aqueous and alcoholic solvents. These compounds are difficult to purify by SFC too as they are equally sensitive to traditional co-solvents like methanol, ethanol, and 2-propanol. 2,2,2 trifluoroethanol (TFE), which has been reported for the purification of a few alcohol sensitive compounds, was evaluated as a co-solvent in this study for the purification of chiral and achiral boronate esters by SFC.

Use of Hybrid Capillary Tube Apparatus on 400 MHz NMR for Quantitation of Crucial Low-Quantity Metabolites Using aSICCO Signal.

Metabolites of new chemical entities can influence safety and efficacy of a molecule and often times need to be quantified in preclinical studies. However, synthetic standards of metabolites are very rarely available in early discovery. Alternate approaches such as biosynthesis need to be explored to generate these metabolites.

A Serum Small Molecule Biosignature of Radiation Exposure from Total Body Irradiated Patients.

The potential for radiological accidents and nuclear terrorism has increased the need for the development of new rapid biodosimetry methods. In addition, in a clinical setting the issue of an individual's radiosensitivity should be taken into consideration during radiotherapy. We utilized metabolomics and lipidomics to investigate changes of metabolites in serum samples following exposure to total body ionizing radiation in humans.

Quantitative NMR: an applicable method for quantitative analysis of medicinal plant extracts and herbal products.

Introduction: Quantitative analysis and standardisation of plant extracts or herbal products is a tedious process requiring time-consuming sample preparation and analytical method development for the resolution of analyte peaks from the complex natural extract. Quantitative analysis by HPLC requires a pure authentic standard of the compound being quantified. We report here a quantitative NMR (qNMR) method for quantitative analysis of three medicinal plant extracts and their herbal products without the need of authentic standards.

One pot synthesis and anticancer activity of dimeric phloroglucinols.

A series of dimeric phloroglucinol compounds were synthesized in a single step using commercially available phloroglucinol and methanesulfonic acid. Based on the reported anticancer activity of plant derived dimeric phloroglucinols, these synthesized compounds were evaluated for their in vitro anti-proliferative activities against various cancer cell lines. Several compounds demonstrated in vitro cytotoxic effects across a wide array of tumor cell types.

Anti-HIV activity of Indian medicinal plants.

Acquired immunodeficiency syndrome patients face great socio-economic difficulties in obtaining treatment. There is an urgent need for new, safe, and cheap anti-HIV agents. Traditional medicinal plants are a valuable source of novel anti-HIV agents and may offer alternatives to expensive medicines in future.

Small molecule HIV entry inhibitors: Part II. Attachment and fusion inhibitors: 2004-2010.

Introduction: The first US FDA approved HIV entry inhibitor drug Enfuvirdine belongs to the fusion inhibitor category. Earlier efforts in this area were focused on peptides and monoclonal antibodies; recently, the focus has shifted towards the development of small molecule HIV attachment and fusion inhibitors. They can be used for prophylactic purposes and also hold potential for the development of HIV microbicides.

Small molecule HIV entry inhibitors: Part I. Chemokine receptor antagonists: 2004 - 2010.

Introduction: HIV/AIDS is one of the most devastating diseases in the world affecting > 40 million people worldwide. Morbidity and mortality from AIDS are significantly reduced due to the advent of highly active antiretroviral therapy (HAART). Long-term toxicity, emergence of drug resistant HIV strains and drug-drug interactions limit the effectiveness of HAART therapy.

Biomimetic synthesis and anti-HIV activity of dimeric phloroglucinols.

Plants are an important source of a variety of bioactive compounds with different modes of action. Anti-HIV agents from plant sources can be useful in developing novel therapies for inhibiting HIV infection. Based on the reported anti-HIV activity of plant derived phloroglucinols, several new dimeric phloroglucinols were synthesized in the present study by varying substitution on aromatic ring and at methylene bridge.

Antiprotozoal and antimicrobial activities of O-alkylated and formylated acylphloroglucinols.

In the present article, we examined the antileishmanial, antimalarial, antibacterial, and antifungal activities of several newly synthesized O-alkylated phloroglucinol compounds (11-19) which are analogues of the naturally occurring antimalarial compound 1. Analogues 12 and 16 exhibited antileishmanial activity against, Leishmania donovani promastigotes with IC(50)s of 5.3 and 4.