TCG Life science Ltd

Saltlake, India

TCG Life science Ltd

Saltlake, India
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Spondias pinnata has been reported for its efficient anticancer effects, but the studies were mostly focused on its extract.Since its bioactive compounds are largely unknown, this study was designed to characterize the lead components present in it and their anticancer activity against human glioblastoma cell line (U87).Major compounds from the ethyl acetate fraction were isolated by column chromatography and their anticancer potentials against U87 cells were evaluated. Furthermore, flow cytometric and immunoblotting analyses were performed to demonstrate the mechanism of apoptosis inducing activity of methyl gallate (MG) against U87 cell line.Four major compounds were isolated from the ethyl acetate fraction. Amongst these, two compounds showed promising activities and with the help of different spectroscopic methods they were identified as gallic acid and MG. Flow cytometric studies revealed that MG-induced apoptosis in U87 cells dose-dependently; the same was confirmed by activation of caspases through cleavage of endogenous substrate poly (adenosine diphosphate-ribose) polymerase. MG treatment also induced the expression of p53 and B-cell lymphoma-2-associated X and cleavage of BH3 interacting-domain with a concomitant decrease in B-cell lymphoma-2 expression. Moreover, MG-induced sustained phosphorylation of extracellular signal-regulated kinase (ERK1/2) in U87 cells with no change in the phosphorylation of other mitogen-activated protein kinases (c-Jun N-terminal of stress-activated protein kinases, p38).MG is a potent antioxidant and it induces sustained ERK1/2 activation and apoptosis in human glioblastoma U87, and provide a rationale for evaluation of MG for other brain carcinoma cell lines for the advancement of glioblastoma therapy.

PubMed | Jadavpur University, Calcutta Institute of Pharmaceutical Technology, Peerless Hospital and TCG Life science Ltd
Type: Journal Article | Journal: The Journal of pharmacy and pharmacology | Year: 2015

This study attempts to investigate the antimicrobial properties of Kalanchoe blossfeldiana with a particular reference to quorum sensing (QS)-mediated biofilm formation.The methanol extract of K.blossfeldiana leaves (MEKB) was evaluated for antimicrobial properties including QS-controlled production of biofilm (including virulence factor, motility and lactone formation) in Pseudomonas aeruginosa. Methanol extract of K.blossfeldiana was also evaluated for anti-cytokine (tumour necrosis factor-alpha, interleukin-6 and interleukin-1 beta) properties in peripheral blood mononuclear cells (PBMC).Methanol extract of K.blossfeldiana exhibited antimicrobial effect on clinical isolates, as well as standard reference strains. Pseudomonas aeruginosa exposed to MEKB (subminimum inhibitory concentration (MIC)) displayed reduced biofilm formation, whereas supra-MIC produced destruction of preformed biofilms. Methanol extract of K.blossfeldiana reduced the secretion of virulence factors (protease and pyoverdin) along with generation of acyl homoserine lactone (AHL). Confocal laser scanning microscopy images indicate reduction of biofilm thickness. The extract also reduced cytokine formation in lipopolysaccharide-stimulated PBMC.Kalanchoe blossfeldiana was found to interfere with AHL production, which in turn may be responsible for downregulating QS-mediated production of biofilm and virulence. This first report on the antibiofilm and anticytokine properties of this plant may open up new vistas for future exploration of this plant for combating biofilm-related resistant infections.

PubMed | Jadavpur University and TCG Life science Ltd.
Type: Journal Article | Journal: Indian journal of pharmacology | Year: 2016

Bruguiera gymnorrhiza (BRG) (L.) Lamk (Rhizophoraceae), a mangrove species, is widely distributed in the Pacific region, eastern Africa, Indian subcontinent, and subtropical Australia. The leaves of this plant are traditionally used for treating burns and inflammatory lesions. This study isolates the bioactive compound from the methanol extract of BRG leaves and evaluates the possible mechanisms of anti-inflammatory activity involved.Bioassay-guided fractionation of BRG was performed to identify the bioactive fraction (displaying inhibition of cyclooxygenase 2 [COX2] - 5-lipoxygenase (5-LOX) activities and tumor necrosis factor-alpha (TNF-) production at the tested concentrations of 100 and 10 g/ml). The fractionation was performed by solvent extraction and preparative high-performance liquid chromatography. The bioactive compound was characterized by ultraviolet-visible, liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. The antioxidant potential was evaluated by electron spin resonance spectrum of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical at 250 M. The effect of the compound was also studied on TNF- converting enzyme and nuclear factor kappa B (NF-B) activities at the concentrations 100, 10 and 1 g/ml.Bioassay-guided purification of BRG revealed the presence of a flavone (5,7-dihydroxy-2- [3-hydroxy-4,5-dimethoxy-phenyl]-chromen-4-one) of molecular weight 330Da. It demonstrated more than 80% inhibition against COX2, 5-LOX activities and TNF- production at 100 g/ml. It also displayed 40% inhibition against DPPH radical at the tested concentration along with 23.1% inhibition of NF-B activity at 100 g/ml.The isolated methoxy-flavone may play a predominant role in the anti-inflammatory properties displayed by BRG leaves. Such activity may involve multiple mechanisms, namely (a) modulation of oxidative stress (b) inhibition of arachidonic acid metabolism and (c) downregulation of pro-inflammatory cytokines probably through NF-B inhibition.

PubMed | Jadavpur University, TCG Life science Ltd. and Indian Institute of Technology Kharagpur
Type: Journal Article | Journal: International journal of pharmaceutics | Year: 2014

Paclitaxel, a potential anticancer agent against solid tumors has been restricted from its oral use due to poor water solubility as well as Pgp efflux property. The present study was aimed to improve the oral bioavailability of paclitaxel through development of (o/w) nanoemulsion consisting of Capryol 90 as internal phase with Tween 20 as emulsifier with water as an external phase. Formulations were selected from the nanoemulsion region of pseudo-ternary phase diagrams, formulated by aqueous titration method. The developed nanoemulsion has been characterized by its thermodynamic stability, morphology, droplet size, zeta potential, viscosity where in vitro release was evaluated through dialysis. Paclitaxel nanoemulsion exhibited thermodynamical stability with low viscosity, nano-sized oil droplets in water with low poly-dispersity index. The shelf life of the paclitaxel nanoemulsion was found to be approximately 2.38 years. Increased permeability through the Caco-2 cell monolayer and decreased efflux is great advantageous for nanoemulsion formulation. The effects of paclitaxel nanoemulsion on breast cancer cell proliferation, morphology and DNA fragmentation were analyzed in vitro which showed significant anti-proliferation and decreased IC50 values in nanoemulsion group which may be due to enhanced uptake of paclitaxel through the oil core. Moreover, the absolute oral bioavailability and sustained release profile of the paclitaxel nanoemulsion evaluated in mouse model was found to improve up to 55.9%. The concentration of paclitaxel in mice plasma was determined by our validated LC-MS/MS method. By reviewing the significant outcome of the present investigation based on stability study, Caco-2 permeability, cell proliferative assay and pharmacokinetic profile it may be concluded that the oral nanoemulsion has got encouraging advantages over the presently available formulations of this injectable chemotherapeutic drug.

Malhotra R.,Guru Jambheshwar University of Science and Technology | Ghosh A.,Guru Jambheshwar University of Science and Technology | Ghosh A.,TCG Life science Ltd | Ghosh R.,Guru Jambheshwar University of Science and Technology | And 9 more authors.
Tetrahedron Asymmetry | Year: 2011

A scalable asymmetric synthesis of trans-2-amino-6,7-dimethoxy-1- phenyltetralin 2 and its N-nosyl derivative 12 have been achieved from Garner aldehyde derived from easily available d-serine using a stereoselective PhMgBr addition, Wittig reaction and TFA-mediated Friedel-Crafts cyclization as the key steps. The synthesis of dihydrexidine is accomplished from the N-nosyl-2-amino-1-phenyltetralin 12. © 2011 Elsevier Ltd. All rights reserved.

Malhotra R.,Guru Jambheshwar University of Science and Technology | Chakrabarti S.,Guru Jambheshwar University of Science and Technology | Chakrabarti S.,TCG Life science Ltd | Ghosh A.,Guru Jambheshwar University of Science and Technology | And 9 more authors.
Tetrahedron Asymmetry | Year: 2013

A divergent and scalable asymmetric synthesis of the dopamine D1 agonists, A-86929, and dihydrexidine with high diastereo- and enantioselectivity was accomplished from Weinreb amide 8 derived from inexpensive and easily available l-serine. The synthesis of A-86929 involves only one chromatographic purification. © 2013 Elsevier Ltd. All rights reserved.

Malhotra R.,Guru Jambheshwar University of Science and Technology | Dey T.K.,Guru Jambheshwar University of Science and Technology | Dey T.K.,TCG Life science Ltd. | Dutta S.,TCG Life science Ltd. | And 2 more authors.
Organic and Biomolecular Chemistry | Year: 2014

First regioselective ring opening of serine derived cyclic sulfamidate by hard nucleophiles like ArONa is developed, where β-elimination of serine sulfamidate ester by stronger nucleophiles is overcome by reversal of the electronic effect of the carboxylate anion. This method provides easy and direct access to a variety of N-Boc- and N-PMB protected β-aryloxy-α-amino acids with complete retention of enantiopurity in moderate to high yields. © the Partner Organisations 2014.

Hajra S.,Indian Institute of Technology Kharagpur | Ghosh R.,TCG Life science Ltd | Ghosh R.,Guru Jambheshwar University of Science and Technology | Chakrabarti S.,TCG Life science Ltd | And 10 more authors.
Advanced Synthesis and Catalysis | Year: 2012

A highly enantioselective (up to 91% ee) rhodium-catalyzed asymmetric addition of arylboronic acids has been achieved leading to the challenging dihydro-3-nitronaphthalenes using one equivalent of phosphoramidite ligand to rhodium catalyst. A concise formal asymmetric synthesis of the dopamine D1 agonist, dihydrexidine was accomplished using the method. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PubMed | Kalyani University and TCG Life Science Ltd.
Type: | Journal: Folia microbiologica | Year: 2017

Increasing bacterial resistance to common drugs is a major public health concern for the treatment of infectious diseases. Certain naturally occurring compounds of plant sources have long been reported to possess potential antimicrobial activity. This study was aimed to investigate the antibacterial activity and possible mechanism of action of andrographolide (Andro), a diterpenoid lactone from a traditional medicinal herb Andrographis paniculata. Extent of antibacterial action was assessed by minimal bactericidal concentration method. Radiolabeled N-acetyl glucosamine, leucine, thymidine, and uridine were used to determine the effect of Andro on the biosyntheses of cell wall, protein, DNA, and RNA, respectively. In addition, anti-biofilm potential of this compound was also tested. Andro showed potential antibacterial activity against most of the tested Gram-positive bacteria. Among those, Staphylococcus aureus was found to be most sensitive with a minimal inhibitory concentration value of 100g/mL. It was found to be bacteriostatic. Specific inhibition of intracellular DNA biosynthesis was observed in a dose-dependent manner in S. aureus. Andro mediated inhibition of biofilm formation by S. aureus was also found. Considering its antimicrobial potency, Andro might be accounted as a promising lead for new antibacterial drug development.

PubMed | Kalyani University, TCG Life Science Ltd. and Visva Bharati
Type: | Journal: Journal of biomedical science | Year: 2016

Breast cancer is considered as an increasing major life-threatening concern among the malignancies encountered globally in females. Traditional therapy is far from satisfactory due to drug resistance and various side effects, thus a search for complementary/alternative medicines from natural sources with lesser side effects is being emphasized. Andrographis paniculata, an oriental, traditional medicinal herb commonly available in Asian countries, has a long history of treating a variety of diseases, such as respiratory infection, fever, bacterial dysentery, diarrhea, inflammation etc. Extracts of this plant showed a wide spectrum of therapeutic effects, such as anti-bacterial, anti-malarial, anti-viral and anti-carcinogenic properties. Andrographolide, a diterpenoid lactone, is the major active component of this plant. This study reports on andrographolide induced apoptosis and its possible mechanism in highly proliferative, invasive breast cancer cells, MDA-MB-231 lacking a functional p53 and estrogen receptor (ER). Furthermore, the pharmacokinetic properties of andrographolide have also been studied in mice following intravenous and oral administration.Andrographolide showed a time- and concentration- dependent inhibitory effect on MDA-MB-231 breast cancer cell proliferation, but the treatment did not affect normal breast epithelial cells, MCF-10A (>80 %). The number of cells in S as well as G2/M phase was increased after 36 h of treatment. Elevated reactive oxygen species (ROS) production with concomitant decrease in Mitochondrial Membrane Potential (MMP) and externalization of phosphatidyl serine were observed. Flow cytometry with Annexin V revealed that the population of apoptotic cells increased with prolonged exposure to andrographolide. Activation of caspase-3 and caspase-9 were also noted. Bax and Apaf-1 expression were notably increased with decreased Bcl-2 and Bcl-xL expression in andrographolide-treated cells. Pharmacokinetic study with andrographolide showed the bioavailability of 9.271.69 % with a Cmax, of 0.730.17 mol/L and Tmax of 0.420.14 h following oral administration. AG showed rapid clearance and moderate terminal half lives (T1/2) of 1.860.21 and 3.300.35 h following IV and oral administration respectively.This investigation indicates that andrographolide might be useful as a possible chemopreventive/chemotherapeutic agent for human breast cancers.

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