Phytochemical screening and antimicrobial potentials of Borreria sps (Rubiaceae)

AbstractSuccessive hexane, acetone, ethanol and methanolic whole plant extracts of the Borreria sps were investigated for phytochemical screening and assessed for antimicrobial activity. Phytochemical analysis of Borreria sps extracts revealed the presence of phenolics, flavonoids and tannins. Among them, Borreria laevicaulis hexane extracts were found to be most effective showing the largest zone of inhibition against Staphylococcus aureus (22.15mm) and Candida albicans (25.65mm). Further studies indicated that the minimum inhibitory concentration of B. laevicaulis hexane extracts was found to be 62.5μg/ml against S. aureus and 250μg/ml against C. albicans and the zone of inhibitions was significantly higher than nystatin (positive control). Together, we provide new insights of the B. laevicaulis as a potential candidate for antimicrobial drug discovery using in vitro studies that might be useful to treat human infectious diseases and antibiotic resistant pathogens

Plant-derived tetranortriterpenoid, methyl angolensate activates apoptosis and prevents ehrlich ascites carcinoma induced tumorigenesis in mice

Background: Cancer is a leading health problem throughout the world. For decades, natural plant products have been playing promising roles as anticancer agents. Objective: The present study aims to investigate the chemotherapeutic potential of Methyl Angolensate (MA), purified from Soymida febrifuga in mice bearing carcinoma and examines the molecular basis for its anticancer actions. Study Design: The inhibitory effects of MA treatment on the survival of mice bearing Carcinoma and adverse side effects of MA treatment in mice were analyzed. Methods: Tumor volume, life span, histopathology, Immunohistochemical (IHC) analysis, estimation of liver enzyme, alkaline phosphatase and metabolites, creatinine and urea. Results: Oral administration of MA in mice with Ehrlich Ascites Carcinoma showed significant inhibition of tumor growth compared to untreated mice. We observed a significant increase in the life span (∼4-fold) of tumor bearing animals following treatment with MA. MA affected tumor cell proliferation by activating intrinsic pathway of apoptosis without imparting any side effect on normal cells. MA treatment in mice showed no major side effects. Conclusion: MA treatment showed significant inhibition of tumor growth by inducing apoptosis as well increased life span of mice, with no adverse side effects to normal cells. Altogether, the present in vivo study provides new insights of MA serving as a cancer chemotherapeutic agent

A natural compound, methyl angolensate, induces mitochondrial pathway of apoptosis in Daudi cells

Natural products discovered from medicinal plants have played an important role in the treatment of cancer. In an effort to identify novel small molecules which can affect the proliferation of lymphoma cells, we tested Methyl Angolensate (MA), a plant derived tetranortriterpenoid, purified from the crude extract of the root callus of Soymida febrifuga commonly known as Indian red wood tree. We have tested MA for its cytotoxic properties on Burkitt’s lymphoma cell lines, using various cellular assays. We observed that MA induces cytotoxicity in Daudi cells in a dose-dependent manner using trypan blue, MTT and LDH assays. We find that the treatment with MA led to activation of DNA double-strand break repair proteins including KU70 and KU80, suggesting the activation of nonhomologous DNA end joining pathway in surviving cells. Further, we find that methyl angolensate could induce apoptosis by cell cycle analysis, annexin V-FITC staining, DNA fragmentation and PARP cleavage. Besides, MA treatment led to reactive oxygen species generation and loss of mitochondrial transmembrane potential. These results suggest the activation of mitochondrial pathway of apoptosis. Hence, we identify MA as a potential chemotherapeutic agent against Daudi cells

5-isopropylidene-3-ethyl rhodanine induce growth inhibition followed by apoptosis in leukemia cells

5-Isopropylidene-3-ethyl rhodanine II was prepared by conventional and Microwave assisted synthesis. For the first time, we found that rhodanine II treatment led to cytotoxicity in leukemic cell line, CEM by inducing apoptosis

Methyl angolensate from callus of Indian redwood induces cytotoxicity in human breast cancer cells

Aim: Natural products discovered from medicinal plants have played an important role in the treatment of cancer. Methyl Angolensate (MA), a tetranortriterpenoid obtained from the root callus of Indian Redwood tree, Soymida febrifuga Roxb. (A.Juss) was tested for its anticancer properties on breast cancer cells. Methods: Cell viability was tested using trypan blue, MTT and LDH assays. Tritiated thymidine assay and flowcytometry were used to study effect of MA on cell proliferation. The activation of apoptosis was checked by annexin V and JC-1 staining followed by FACS analysis. Immunoblotting analysis was used for studying expression of apoptotic and DNA double strand break repair proteins. Results: We find that MA inhibited the growth of breast cancer cell line, T47D in a time- and dose-dependent manner. MA treatment led to the inhibition of cell proliferation as detected by tritiated thymidine assay and flowcytometry. Further, MA treated cells exhibited typical apoptotic morphological changes and led to the accumulation of subG1 peak in cell cycle distribution. The induction of apoptosis was further confirmed both by annexin V staining and JC1 staining. We also find that MA activates MAP kinase pathway to induce apoptosis. Besides, we find a time dependent activation followed by degradation of DNA double-strand break repair proteins upon treatment with MA. Conclusion: These results suggest that MA induces cytotoxicity in breast cancer cells. Further, the altered expression of DSB repair proteins in MA treated cells may control the induction of apoptosis in these cancer cells

Phytochemicals and antimicrobial potentials of mahogany family

Drug resistance to human infectious diseases caused by pathogens lead to premature deaths through out the world. Plants are sources for wide variety of drugs used for treating various diseases. Systematic screening of medicinal plants for the search of new antimicrobial drug candidates that can inhibit the growth of pathogens or kill with no toxicity to host is being continued by many laboratories. Here we review the phytochemical investigations and biological activities of Meliaceae. The mahogany (Meliaceae) is family of timber trees with rich source for limonoids. So far, amongst the different members of Meliaceae, Azadirachta indica and Melia dubia have been identified as the potential plant systems possessing a vast array of biologically active compounds which are chemically diverse and structurally complex. Despite biological activities on different taxa of Meliaceae have been carried out, the information of antibacterial and antifungal activity is a meager with exception to Azadirachta indica. Together we provide new insights of Meliaceae members demonstrating as a potential source as antimicrobial agents using in vitro studies

Biochemical Characterization of Kat1 : a Domesticated hAT-Transposase that Induces DNA Hairpin Formation and MAT-Switching

Kluyveromyces lactis hAT-transposase 1 (Kat1) generates hairpin-capped DNA double strand breaks leading to MAT-switching (MATa to MAT alpha). Using purified Kat1, we demonstrate the importance of terminal inverted repeats and subterminal repeats for its endonuclease activity. Kat1 promoted joining of the transposon end into a target DNA molecule in vitro, a biochemical feature that ties Kat1 to transposases. Gas-phase Electrophoretic Mobility Macromolecule analysis revealed that Kat1 can form hexamers when complexed with DNA. Kat1 point mutants were generated in conserved positions to explore structure-function relationships. Mutants of predicted catalytic residues abolished both DNA cleavage and strand-transfer. Interestingly, W576A predicted to be impaired for hairpin formation, was active for DNA cleavage and supported wild type levels of mating-type switching. In contrast, the conserved CXXH motif was critical for hairpin formation because Kat1 C402A/H405A completely blocked hairpinning and switching, but still generated nicks in the DNA. Mutations in the BED zinc-finger domain (C130A/C133A) resulted in an unspecific nuclease activity, presumably due to nonspecific DNA interaction. Kat1 mutants that were defective for cleavage in vitro were also defective for mating-type switching. Collectively, this study reveals Kat1 sharing extensive biochemical similarities with cut and paste transposons despite being domesticated and evolutionary diverged from active transposons

Phytochemical and antimicrobial studies of methyl angolensate and luteolin-7-O-glucoside isolated from callus cultures of Soymida febrifuga

Soymida febrifuga (Roxb.) A. Juss. is an indigenous lofty deciduous medicinal tree, monotypic genus endemic to India. Hexane, ethyl acetate and methanol extracts of Soymida febrifuga root callus were tested for their phytochemical constituents and antimicrobial activity. Among them, ethyl acetate extract was found to be most effective, which on subjection to silica gel column chromatography led to the separation and isolation of methyl angolensate and luteolin-7-O-glucoside. Structures were determined by Nuclear Magnetic Resonance and Liquid Chromatographic Mass Spectroscopic methods. Further studies indicated that methyl angolensate and luteolin-7-O-glucoside had an anti-bacterial effect against Bacillus subtilis and Salmonella typhimurium, respectively. In addition to that methyl angolensate had an anti-fungal activity against Aspergillus niger while luteolin-7-O-glucoside inhibited Alternaria alternata

Extracts of Strawberry Fruits Induce Intrinsic Pathway of Apoptosis in Breast Cancer Cells and Inhibits Tumor Progression in Mice

Background: The consumption of berry fruits, including strawberries, has been suggested to have beneficial effects against oxidative stress mediated diseases. Berries contain multiple phenolic compounds and secondary metabolites that contribute to their biological properties. Methodology/Principal Findings: Current study investigates the anticancer activity of the methanolic extract of strawberry (MESB) fruits in leukaemia (CEM) and breast cancer (T47D) cell lines ex vivo, and its cancer therapeutic and chemopreventive potential in mice models. Results of MTT, trypan blue and LDH assays suggested that MESB can induce cytotoxicity in cancer cells, irrespective of origin, in a concentration-and time-dependent manner. Treatment of mice bearing breast adenocarcinoma with MESB blocked the proliferation of tumor cells in a time-dependent manner and resulted in extended life span. Histological and immunohistochemical studies suggest that MESB treatment affected tumor cell proliferation by activating apoptosis and did not result in any side effects. Finally, we show that MESB can induce intrinsic pathway of apoptosis by activating p73 in breast cancer cells, when tumor suppressor gene p53 is mutated. Conclusions/Significance: The present study reveals that strawberry fruits possess both cancer preventive and therapeutic values and we discuss the mechanism by which it is achieved

Synthesis and biological evaluation of novel 1-(4-methoxyphenethyl)-1H-benzimidazole-5-carboxylic acid derivatives and their precursors as antileukemic agents

We report here the synthesis and preliminary evaluation of novel 1-(4-methoxyphenethyl)-1H-benzimidazole-5-carboxylic acid derivatives 6(a-k) and their precursors 5(a-k) as potential chemotherapeutic agents. In each case, the structures of the compounds were determined by FTIR, H-1 NMR and mass spectroscopy. Among the synthesized molecules, methyl 1-(4-methoxyphenethyl)-2-(4-fluoro-3-nitrophenyl)-1H-benzimidazole-5-car boxylate (5a) induced maximum cell death in leukemic cells with an IC50 value of 3 mu M. Using FACS analysis we show that the compound 5a induces S/G2 cell cycle arrest, which was further supported by the observed down regulation of CDK2, Cyclin B1 and PCNA. The observed downregulation of proapoptotic proteins, upregulation of antiapoptotic proteins, cleavage of PARP and elevated levels of DNA strand breaks indicated the activation of apoptosis by 5a. These results suggest that 5a could be a potent anti-leukemic agent. (C) 2009 Elsevier Ltd. All rights reserved