Inhibitory role of a smart nano-trifattyglyceride of Moringa oleifera root in epithelial ovarian cancer, through attenuation of FSHR - c-Myc axis.

BACKGROUND AND AIM: Epithelial ovarian cancer has the deadliest prognosis amongst gynaecological cancers, warranting an unmet need for newer drug targets. Based on its anticancer as well as abortifacient potential, Moringa oleifera Lam. root was hypothesized to have some implications in follicle stimulating hormone receptor (FSHR) dependent cancers like epithelial ovarian cancer. EXPERIMENTAL PROCEDURE: Effect of Moringa oleifera Lam. root extract (MRE) was studied in epithelial ovarian cancer cell line through in vitro studies viz. MTT assay, clonogenic assay, cell cycle analysis, flow cytometry, western blot analysis, immunocytochemical analysis of FSHRand c-Myc expression and in vivo studies viz. effect of MRE in mice model of ovarian carcinoma. The structure of the active compound of MRE was elucidated following solvent extraction, purification through column chromatography, preparative TLC and bioactivity guided structural identification through 1H-NMR, 13C-NMR, DEPT-135, ESIMS,FT-IR spectrophotometry, UV-vis-NIR spectrophotometry and DFT study. RESULTS AND CONCLUSION: Crude MRE displayed cytotoxic activity, induced apoptosis, and attenuated expression of FSHR and c-Myc in ovarian cancer cell line OAW42. MRE also attenuated expression of CD31, FSHR, and c-Myc in tumour xenograft mouse model. Finally, the active compound purified from ethyl acetate-n-hexane subfraction ofMRE, that attenuated viability of ovarian carcinoma cell lines and reduced FSHR and c-Myc expression, was identified as a naturally hydrated-trifattyglyceride, showing aDFT-optimized folded amphipathic structure for easy transportation through hydrophilic and hydrophobic regions in a biological system, indicating its immense therapeutic relevance in epithelial ovarian carcinoma.

Evaluation of a new flow cytometry based method for detection of BCR-ABL1 fusion protein in chronic myeloid leukemia.

BACKGROUND: Philadelphia chromosome, a hallmark of chronic myeloid leukemia (CML), plays a key role in disease pathogenesis. It reflects a balanced reciprocal translocation between long arms of chromosomes 9 and 22 involving BCR and ABL1 genes, respectively. An accurate and reliable detection of BCR-ABL fusion gene is necessary for the diagnosis and monitoring of CML. Previously, many technologies, most of which are laborious and time consuming, have been developed to detect BCR-ABL chimeric gene or chromosome. METHODS: A new flow cytometric immunobead assay was used for detection of BCR-ABL fusion proteins and applicability, sensitivity, reliability, efficacy and rapidity of this method was evaluated. RESULTS: From February 2009 to January 2014, a total 648 CML patients were investigated for the status of BCR-ABL1 protein. Among them, 83 patients were enrolled for comparative study of BCR-ABL1 positivity by three routinely used procedures like karyotyping, and quantitative real time PCR (RT-PCR) as well as immunobead flow cytometry assay. BCR-ABL protein analysis was found consistent, more sensitive (17% greater sensitivity) and reliable than the conventional cytogenetics, as flow cytometry showed 95% concordance rate to RT-PCR. CONCLUSION: BCR-ABL fusion protein assay using a new flow cytometric immunobead might be useful in the diagnosis and monitoring CML patients.

Mugineic acid, active ingredient of wheat grass: an oral novel hexadentate iron chelator in iron overloaded diseases.

Iron chelation therapies are required for the treatment of iron overloaded patients; nonetheless, their side effects are also well known. We have evaluated iron-chelating activity of wheat grass extract (WHE) and its purified compound, mugineic acid in murine model with phenylhydrazine (PHZ) and dextran induced acute and chronic iron overload conditions. PHZ and dextran treatment induced acute and chronic iron overload condition in mice, respectively, as indicated by increased serum and tissue iron in both cases. Iron overload was also accompanied with haemosiderosis in tissues (liver and spleen). These PHZ and dextran -: treated mice were orally treated with either crude WHE or purified mugineic acid. The efficacy of mugineic acid and WHE was compared with the potent oral iron chelator ICL670 (Exjade). PHZ and dextran treatment followed by oral administration of WHE or mugineic acid significantly checked the rise of serum/plasma levels of iron as well as tissue iron and also, haemosiderosis in tissues. The results are highly comparable with known iron chelator ICL670. WHE and purified mugineic acid, both seem to have significant prospect to be the cheap, non-toxic, hexadentate and oral therapeutic agents to prevent or alleviate toxic iron overload in patients.

Antioxidative and anticarcinogenic activities of methylpheophorbide a, isolated from wheat grass (Triticum aestivum Linn.).

Methylphophorbide a (MPa) has been isolated from the ethanol extract of the wheat grass plant. Its antioxidative efficacy is evaluated by hydroxyl radical scavenging activities and reducing capacity which are significantly up regulated in comparison with aqueous extract of the plant. The compound shows iron-binding capacity where the Fe(2+) binds with MPa by two types of binding patterns with dissociation constants 157.17 and 27.89. It has antioxidative and cytotoxic effects on HeLa and Hep G2 cells. The cancerous cell survivability decreases with increasing concentration of MPa. These findings have provided evidence for the traditional use of the wheat grass plant in the treatment of cancers, oxidative stress and iron overloaded disorders.

The Potential Utility of Acceptance and Commitment Therapy (ACT) for Reducing Stress and Improving Wellbeing in Cancer Patients in Kolkata.

As soon as a patient comes to know that he/she has cancer, the stress starts and psychological intervention is required. The authors assessed how well a cancer patient can manage stress over the course of the psychological intervention. Data was collected among 107 patients during pre and post intervention and at 2 months follow-up. Intervention was required to measures include acceptance of the disease, managing stress, well -being, and meaning of life. Finally, effects of acceptance and commitment therapy (ACT) were defined in acceptance measured in terms of a significant difference between pre and post intervention scores in the meaning of life and the acceptance level. This acceptance and commitment therapy can be an effective intervention approach for cancer patients that increases acceptance regarding disease and simultaneously leads to improvement in the meaning of life.

Acute toxicity test of a natural iron chelator and an antioxidant, extracted from Triticum aestivum Linn. (wheat grass).

Triticum aestivum (wheat grass) is widely used in traditional medicine to treat various diseases. Previously the purified compounds and crude extract of T. aestivum were established to have iron chelation potency and antioxidant activity. So it is necessary to evaluate the toxic properties of any compound isolated from plant extract to prevent any untoward side effects. The aim of this study was to determine the acute oral toxicity level of our purified compounds, i.e. mugineic acids and methylpheophorbide a., and crude extract of T. aestivum, on Swiss albino mice at dosage of 2000 mg/kg for a period of 14 days using the organisation for economic co-operation and development guidelines 423. There was no mortality. No change in behavioural pattern, clinical signs, body weight and blood biochemistry profile were observed. Kidney and liver showed normal histo-pathological architecture. Hence, the oral administration of compounds and extract of T. aestivum did not produce any significant toxic effect on mice. Thus we may conclude that the extract can be utilised for pharmaceutical formulations as iron chelator and antioxidant agent for various diseases.

A room temperature copper catalyzed N-selective arylation of ß-amino alcohols with iodoanilines and aryl iodides.

An efficient method is described for the synthesis of N-(2-aminophenyl)-2-hydroxyethylamines via a copper catalyzed N-selective arylation of ß-amino alcohols with iodoanilines. The corresponding coupling products are useful intermediates for the synthesis of a variety of N-2-hydroxyethyl-substituted benzimidazoles, benzimidazolones, and iminobenzimidazoles. We found that 2-iodoaniline only arylates certain amino alcohols but not amines lacking a hydroxyl group. We also demonstrate the arylation of sterically demanding ß-amino alcohols, such as ephedrine and prolinol with aryl iodides at room temperature.

SAR Based Optimization of a 4-Quinoline Carboxylic Acid Analog with Potent Anti-Viral Activity.

It is established that drugs targeting viral proteins are at risk of generating resistant strains. However, drugs targeting host factors can potentially avoid this problem. Herein we report structure-activity relationship studies leading to the discovery of a very potent lead compound 6-fluoro-2-(5-isopropyl-2-methyl-4-phenoxyphenyl)quinoline-4-carboxylic acid (C44) that inhibits human dihydroorotate dehydrogenase (DHODH) with an IC50 of 1 nM, and viral replication of VSV and WSN-Influenza with an EC50 of 2 nM and 41 nM. We also solved the X-ray structure of human DHODH bound to C44, providing structural insight into the potent inhibition of biaryl ether analogs of brequinar.

Inhibition of pyrimidine synthesis reverses viral virulence factor-mediated block of mRNA nuclear export.

The NS1 protein of influenza virus is a major virulence factor essential for virus replication, as it redirects the host cell to promote viral protein expression. NS1 inhibits cellular messenger ribonucleic acid (mRNA) processing and export, down-regulating host gene expression and enhancing viral gene expression. We report in this paper the identification of a nontoxic quinoline carboxylic acid that reverts the inhibition of mRNA nuclear export by NS1, in the absence or presence of the virus. This quinoline carboxylic acid directly inhibited dihydroorotate dehydrogenase (DHODH), a host enzyme required for de novo pyrimidine biosynthesis, and partially reduced pyrimidine levels. This effect induced NXF1 expression, which promoted mRNA nuclear export in the presence of NS1. The release of NS1-mediated mRNA export block by DHODH inhibition also occurred in the presence of vesicular stomatitis virus M (matrix) protein, another viral inhibitor of mRNA export. This reversal of mRNA export block allowed expression of antiviral factors. Thus, pyrimidines play a necessary role in the inhibition of mRNA nuclear export by virulence factors.

Rapid and efficient entry to vinyl silanes from aldehydes employing a novel metalation-Peterson sequence.

Bis(trimethylsilyl)chloromethane undergoes a rapid and selective metalation with s-BuLi, yielding the nucleophilic bis(trimethylsilyl)methyl anion and providing a straightforward general entry to vinyl silanes from aromatic, aliphatic and vinyl aldehydes.