Eaton’s reagent catalysed alacritous synthesis of 3-benzazepinones

An expeditious method for the synthesis of 3-benzazepinones has been developed by using a mixture of phosphorus pentoxide-methane sulfonic acid (Eaton’s reagent) at room temperature under solvent and metal catalyst free condition. Wide functional group tolerance, mild reaction conditions, simple procedure, ease of work-up and high yields is the citable features of this protocol

Purification and biochemical characterization of a novel secretory dipeptidyl peptidase IV from porcine serum

Purification of DPP-IV enzyme from porcine serum, is presented in this study for the first time. The high molecular weight DPP-IV from porcine serum was fractioned using Sephadex G-75 gel filtration followed by DEAE Sephadex anion exchange and Sephadex G-100 gel filtration chromatography columns with a final yield of 11.25%. The SDS-PAGE of the purified sample showed a single band of molecular mass nearing 160 kDa. Distinct single band was observed after PAS staining confirmed it to be a glycoprotein. The purified enzyme showed an optimum pH and temperature of 8 and 37 degrees C, respectively. The enzyme effectively cleaved fluorogenic substrate Gly-Pro-AMC with Km and Vmax of 4.578 mu M and 90.84 nmoles/min, respectively. Purified DPP-IV activity was inhibited by Diprotin A with an IC(50)value of 8.473 mu M. Among the three plant extracts used to study DPP-IV inhibition, the aqueous hot extract ofTerminalia chebulashowed the highest inhibition of 87.19%, followed by the aqueous cold extract ofMomordica carantia, ( 31.6%) andAzadirachta indica(34.16%) at the concentration of 25 mu g

LATICIFEROUS PLANT PROTEASES IN WOUND CARE

Context: Since antiquity, different parts of plants such as bark, stem and leaves have been used in wound healing. Around 10% of the angiosperm plants produce a natural polymer from specialized laticiferous cells called latex. The major role played by the latex is in wound healing and defensive mechanism against infectious diseases in plants.Objective: This paper emphasizes the role of various plant latex proteases in wound healing. The review also emphasizes on the methodology to be adopted in accessing the proteases studied for procoagulant and thrombolytic activities.Methods: This review conglomerates the reports of laticiferous plants of different families viz., Altingiaceae, Amaranthaceae, Apocyanaceae, Asclepiadaceae, Asteraceae, Caricaceae, Dipterocarpaceae, Euphorbiaceae, Lamiaceae, Moraceae, Papaveraceae, Plumbaginaceae, and Solanaceae involved in wound healing. Emphasis was given on the all possible reports on laticiferous plants in wound healing with thorough literature survey.Results: A number of proteases have been studied from plant latex proteases for their role in wound healing. Some have been extensively studied with characterization while some are yet to be explored. This review enables a detailed up-to-date knowledge of laticiferous plants studied scientifically for wound care.Conclusion: In the past 20 years, with biochemical and pharmacological characterization of plant latex it has come to light that proteases are involved in wound healing. However, research on latex protease is still in budding stage. Adopting the proteases having promising applicability in wound care needs to be focussed.Â

Synthesis and biological evaluation of tetrahydropyridinepyrazoles ('PFPs') as inhibitors of STAT3 phosphorylation

The transcription factor STAT3 is constitutively overexpressed in many human tumors and hence represents a putative target for anticancer drug design. In this work, we describe the synthesis and biological evaluation of a novel chemotype, pyridine-fused pyrazoles ('PFPs') as inhibitors of STAT3 phosphorylation. The effect of the compounds synthesized was evaluated in cell proliferation assays of MCF-7 and HepG2 cancer cell lines and two of the compounds tested (12g and 12k) were found to show significant activity. Both compounds were also found to inhibit the proliferation of Hep3B, HUH-7 and PLC/PRF5 HCC cells in a dose-and time-dependent manner. Furthermore, we established in a DNA binding assay that one of the compounds (12g) was able to significantly inhibit the DNA binding ability of STAT3. Cytotoxicity of 12g against PC3 cells, which do not constitutively phosphorylate STAT3, was found to be minimal, hence lending further support for our mode-of-action hypothesis of this compound. We established for this structure a complete inhibition of CXCL12-induced cell invasion and associated wound healing in HCCLM3 cells, corroborating the proposed modulation of the STAT3 axis by 12g. Finally, molecular modeling was employed to evaluate the hypothesis of PFPs to bind to the SH2 domain of STAT3. Given the efficacy of PFPs in the biological systems studied here we propose their further evaluation in the context of STAT3-mediated cancer therapy

Plumbagin inhibits invasion and migration of breast and gastric cancer cells by downregulating the expression of chemokine receptor CXCR4

<p>Abstract</p> <p>Background</p> <p>Increasing evidence indicates that the interaction between the CXC chemokine receptor-4 (CXCR4) and its ligand CXCL12 is critical in the process of metastasis that accounts for more than 90% of cancer-related deaths. Thus, novel agents that can downregulate the CXCR4/CXCL12 axis have therapeutic potential in inhibiting cancer metastasis.</p> <p>Methods</p> <p>In this report, we investigated the potential of an agent, plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone), for its ability to modulate CXCR4 expression and function in various tumor cells using Western blot analysis, DNA binding assay, transient transfection, real time PCR analysis, chromatin immunoprecipitation, and cellular migration and invasion assays.</p> <p>Results</p> <p>We found that plumbagin downregulated the expression of CXCR4 in breast cancer cells irrespective of their HER2 status. The decrease in CXCR4 expression induced by plumbagin was not cell type-specific as the inhibition also occurred in gastric, lung, renal, oral, and hepatocellular tumor cell lines. Neither proteasome inhibition nor lysosomal stabilization had any effect on plumbagin-induced decrease in CXCR4 expression. Detailed study of the underlying molecular mechanism(s) revealed that the regulation of the downregulation of CXCR4 was at the transcriptional level, as indicated by downregulation of mRNA expression, inhibition of NF-κB activation, and suppression of chromatin immunoprecipitation activity. In addition, using a virtual, predictive, functional proteomics-based tumor pathway platform, we tested the hypothesis that NF-κB inhibition by plumbagin causes the decrease in CXCR4 and other metastatic genes. Suppression of CXCR4 expression by plumbagin was found to correlate with the inhibition of CXCL12-induced migration and invasion of both breast and gastric cancer cells.</p> <p>Conclusions</p> <p>Overall, our results indicate, for the first time, that plumbagin is a novel blocker of CXCR4 expression and thus has the potential to suppress metastasis of cancer.</p

Novel synthesis of N-unsubstituted imidazoles via the cycloaddition of N-(tert-butylsulfinyl)imines and TosMIC

A facile and efficient method was developed for the synthesis of N-unsubstituted imidazoles via the cycloaddition of N-sulfinyl imines and p-toluenesulfonylmethyl isocyanide (TosMIC). This methodology is operationally simple and useful for the preparation of various aromatic and heteroaromatic imidazoles in good to excellent yields. (C) 2020 Published by Elsevier Ltd

A mild and efficient method for the deprotection of trimethyl silyl alkynes using sodium ascorbate and copper sulphate

A competent and fast method for the deprotection of trimethyl silyl group was attained by using cheap, easily accessible, and nontoxic sodium ascorbate in combination with copper sulphate. The method labored was simple and effective for the cleavage of trimethyl silyl group from the protected trimethyl silyl alkynes to their corresponding alkyne derivatives. Wide functional group tolerance, shorter time period, simple procedure and high yields are the striking features of this protocol

A novel and expeditious synthesis of oxazolidinone drugs linezolid and eperezolid

A concise and efficient synthesis of linezolid and eperezolid were accomplished through a convergent scheme utilizing diverse reaction conditions. The synthesis demonstrates utility of a new approach to facilitate the expeditious construction of 3-aryl-5-(substituted methyl)-2-oxazolidinones and easier insertion of N-acetyl group. This new approach offers the possibility of accessing related 2-oxazolidinone members easily as well as making additional analogues of Linezolid. The adopted method afforded high purity and excellent yield compared to other existing synthetic methods. The compounds were successfully characterized by known spectroscopic techniques

1,8-Diazabicyclo5.4.0]undec-7-ene-mediated formation of N-sulfinyl imines

A facile and efficient method was developed for the preparation of a variety of aryl, heteroaryl, and alkyl N-sulfinyl imines using 1,8-diazabicyclo5.4.0]undec-7-ene. In addition to tert-butanesulfinamide, the condensation is also effective with p-toluenesulfinamide. The reaction was performed at room temperature and produces the corresponding N-sulfinyl imines in excellent yields in the absence of acids, metals, and additives. This methodology is also useful for the preparation of N-sulfinyl imines on gram scale. A one-pot synthesis was developed using aryl and heteroaryl alcohols with both tert-butanesulfinamide and p-toluenesulfinamide at room temperature, resulting in the corresponding N-sulfinyl imines with good yields