Comprehensive Analysis of Secondary Metabolites in Usnea longissima (Lichenized Ascomycetes, Parmeliaceae) Using UPLC-ESI-QTOF-MS/MS and Pro-Apoptotic Activity of Barbatic Acid.

Considering the importance of ultra-performance liquid chromatography-electrospray ionization-quadrupole time of flight-tandem mass spectrometry (UPLC-ESI-QTOF-MS/MS) hyphenated techniques for analysis of secondary metabolites from crude extracts, the present study was aimed at identification of secondary metabolites in acetone extract of the lichen Usnea longissima. From our study, 19 compounds were tentatively identified through comparison of exact molecular masses from their MS/MS spectra, mass fragmentation studies and comparison with literature data. In addition, potent cytotoxic activity of U. longissima extract prompted us to isolate four compounds, 18R-hydroxy-dihydroalloprotolichesterinic acid (19), neuropogolic acid (20), barbatic acid (21), and usnic acid (22) from this extract which were adequately identified through mass spectrometry and NMR spectroscopy. All four compounds displayed cytotoxic activity. Barbatic acid (21) manifested doxorubicin equivalent activity against A549 lung cancer cell line with IC50 of 1.78 µM and strong G0/G1 accumulation of cells. Poly ADP-ribose polymerase (PARP) cleavage confirmed that it induced cytotoxic activity via apoptosis. Finally, our work has discerned the depside, barbatic acid (21) from crude extract as a candidate anti-cancer molecule, which induces cell death by stepping up apoptosis.

New cycloartane type-triterpenoids from the areal parts of Caragana sukiensis and their biological activities.

A comprehensive re-investigation of aerial parts of Caragana sukiensis resulted in the isolation of twelve compounds (1-12) including three new cycloartane type triterpenoids (3-5) respectively. Chemical structures of the isolated compounds were established by analysis of their IR, HRMSESI, 1D and 2D NMR spectroscopic data. In addition, these compounds were evaluated for their cytotoxic activity against cancer lines (HeLa, A549, MCF-7, DU-145) and Human embryonic kidney cell line (HEK-293). The results indicated that compound 8 showed potent cytotoxic activity against A549 with IC50 value of 1.54 µM which is comparable to standard drug, doxorubicin. Further, flow cytometric analysis showed that compound 8 arrested the cell cycle in the Go/G1 phase leading to apoptotic cell death. In addition, Hoechst 33258 staining, Annexin V-FITC assay and measurement of mitochondrial membrane potential also suggested that 8 induced cell death by apoptosis. Further, all the isolates were also screened for their antifeedant and insecticidal activity against tobacco caterpillar (Spodoptera litura), using no-choice leaf disk method. Among screened compounds 1, 3, 4, and 6 showed potent antifeedancy with ED50 values of 0.59, 1.19, 0.67, and 1.68 µg/cm2. Overall, this study identified a novel class of cycloartane tritepenoids as potent cyotoxic agents as well as antifeedants.

Synthesis of dihydrosterculic acid-based monoglucosyl diacylglycerol and its analogues and their biological evaluation.

In the present study, Lactobacillus plantarum glycolipid (GL1) molecule in ß-configuration and its fatty acid analogues were synthesized using trichloroacetimidate methodology. The ß-configuration of the GL1 molecule was unambiguously assigned by NMR studies using 2D-ROESY (NOE) and J-coupling analysis. Dihydrosterculic acid was synthesized using Furukawa's reagent and the selective esterification of dihydrosterculic acid at C-3 position of glycerol was achieved with EDC-HCl at 0 °C. In vitro cytotoxicity of the GL1 molecule and its fatty acid analogues was evaluated against DU145, A549, SKOV3 and MCF7 cell lines. Among all the synthesized molecules, the GL1 molecule and compound 7d showed moderate activity, while the compound 7b showed promising activity against all the tested cell lines with IC50 values of 20.1, 18.2, 19.1 and 17.6 µM, respectively. In addition, all tested compounds showed poor cytotoxicity against normal HUVEC cells. The MCF7 cells when treated with compound 7b showed lower bromodeoxyuridine incorporation levels as compared to untreated cells, suggesting that the compound 7b was highly effective and inhibited the cell proliferation. In addition, the compounds showed significant increase in caspases 3 and 9 levels by inducing apoptosis in MCF 7 cells.

Novel cycloartane triterpenoids from the Nepal native plant Caragana sukiensis.

A phytochemical study on the arial part of Caragana sukiensis resulted in the isolation of three new cycloartane triterpenoids 1-3 and their structures were fully established on the basis of detailed spectroscopic (especially 2D NMR and Mass) analysis. These new compounds possessed hemiacetal fused tetrahydropyran rings at C-15/C-16, while 2 and 3 also contains d-xylose moiety.

Establishment and characterization of a fin cell line from Indian walking catfish, Clarias batrachus (L.).

A new cell line, Indian Catfish Fin, derived from the fin tissue of Indian walking catfish, Clarias batrachus, was established and characterized. The cell line grew well in Leibovitz's L-15 medium supplemented with 15% foetal bovine serum (FBS) and has been subcultured more than 110 times since its initiation in 2007. The cells were able to grow at a range of temperature from 28 to 37 °C with optimal growth at 28 °C. The cell line predominantly consists of fibroblast-like cells. The growth rate of fin cells increased as the FBS concentration increased from 2% to 20% at 28 °C with optimum growth at a concentration of 15% or 20% and poor growth at a concentration of 5%. The cells were found to be susceptible to fish nodavirus and IPNV-ab and infection was confirmed by cytopathic effect and reverse transcriptase-polymerase chain reaction. PCR amplification of mitochondrial 12S rRNA using primers specific to C. batrachus confirmed the catfish origin of the cell line. The cell line was characterized further by immunocytochemistry, transfection efficiency with pEGFP-N1 and cell cycle analysis by fluorescent-activated cell sorting.

GSK3beta: role in therapeutic landscape and development of modulators.

Glycogen synthase kinase-3 beta (GSK3beta) is a multifunctional serine/threonine kinase which was originally identified as a regulator of glycogen metabolism. It plays a key role in the regulation of numerous signalling pathways including cellular process such as cell cycle, inflammation and cell proliferation. Over the last few years there is a considerable rise in the number of journals and patents publication by different workers worldwide. Many pharmaceutical companies are focusing on GSK3beta as a therapeutic target for the treatment of disease conditions. The present review is focused on signalling pathways of different disease conditions where GSK3beta is implicated. In this review, we present a comprehensive map of GSK3beta signalling pathways in disease physiologies. Structural analysis of GSK3beta along with molecular modelling reports from numerous workers are reviewed in context of design and development of GSK3beta inhibitors. Patent landscape of the small molecule modulators is profiled. The chemo space for small molecule modulators extracted from public and proprietary Kinase Chembiobase for GSK3beta are discussed. Compounds in different clinical phases of discovery are analysed. The review ends with the overall status of this important therapeutic target and challenges in development of its modulators.

Morbid jealousy in alcoholism.

BACKGROUND: Morbid jealousy is an incompletely understood syndrome. The association between morbid jealousy and alcoholism is unclear. METHOD: Morbid jealousy was assessed in 207 male patients with alcohol dependence (DSM-III-R) using a semi-structured interview schedule administered both to patients and their spouses. RESULTS: Thirty-four per cent (71 out of 207) suffered from morbid jealousy. Morbid jealousy had different manifestations. Some patients expressed it only when intoxicated, others even when sober and in some the jealousy took the form of a delusional disorder. CONCLUSIONS: Alcoholism appears to have an aetiological role in the development of morbid jealousy. Detecting morbid jealousy when it is expressed only under the influence of alcohol has preventive implications.

Clinical profile of STD clinic patients seropositive for HIV antibodies.

PIP: This article provides clinical profiles for HIV seropositive patients discovered at an STD clinic in Tirupati, India. Considering that sexual contact is the most common mode of transmission of HIV, researchers from the SV Medical College at Tirupati conducted a surveillance for HIV infection among patients attending an STD clinic. From January 1988 to April 1989, the researchers collected serum samples from 2320 patients. 11 people were found to be infected with HIV, 1 of whom exhibited the AIDS Related Complex (ARC). 9 out the HIV-infected patients were 20-30 year-old males categorized as heterosexually promiscuous; the remaining 2 seropositive patients were female prostitutes. The seropositivity rate among heterosexually promiscuous males was 0.58%, and 6.7% among female prostitutes (the total seropositivity rate was 0.47%). Among the HIV-infected patients, the most commonly associated STD was syphilis. 5 of the patients had syphilis alone, and 2 others had syphilis and another STD. One of the HIV-infected patients, a 50 year-old heterosexual male with a history of multiple partners, suffered from a nonhealing genital ulcer and inguinal buboes of 1 month duration. A biopsy of the genital ulcer revealed a pattern consistent with that of granuloma venereum. He also developed angular stomatitis which did not respond to B complex therapy. Furthermore, suffering from persistent lymphadenopathy, weight loss, slight thrombo-cytopenia, an opportunistic infection in the form of oral candidosis and persistent seropositivity for HIV antibodies, the patient was deemed to have the AIDS Related Complex. Tirupati's seropositivity rate of .47% was higher that noticed in other parts of the country, leading the authors call for a plan to investigate the problems of HIV-infected people.^ieng

Sarcoidosis of the central nervous system.

A case of central nervous system sarcoidosis verified by direct biopsy and skin tests and without evidence of any other system involvement is reported. The computed tomography findings are described in detail.

Giant aneurysm of anterior communicating artery simulating 3rd ventricular tumor.

This is a case report of an anterior communicating artery aneurysm simulating a 3rd ventricular tumor with obstructive hydrocephalus demonstrated on CT scan. Angiography showed the "tumor" to be an aneurysm. We believe that giant aneurysms of the anterior communicating artery should be included in the differential diagnosis of suspected 3rd ventricular tumors along with suprasellar masses as seen on CT scans.