Crispene A, B, C and D, Four New Clerodane Type Furanoid Diterpenes from Tinospora crispa (L.).

BACKGROUND: Tinospora crispa (L.) is used to alleviate the symptoms of diabetes mellitus in folk medicine. It is also used for hypertension and to treat malaria, remedy for diarrhea, and as vermifuge. MATERIALS AND METHODS: Stems of T. crispa were collected, sun dried for several days followed by oven dried for 24 h at a considerably low temperature and then ground into coarse powder. The powdered stems were soaked in methanol at room temperature for 14 days with occasional shaking. The extract was collected by filtration, and the solvent was evaporated under reduced pressure in a rotary evaporator to obtain a solid residue which was then subjected to fractionation using the modified Kupchan partitioning method into n-hexane, CCl4, CHCl3 and aqueous soluble fractions. The n-hexane soluble fraction was chromatographed over sephadex (LH-20) and the column was eluted with n-hexane: CH2Cl2:MeOH (2:5:1) followed by CH2Cl2:MeOH (9:1) and MeOH (100%) in order to increase the polarities. The column fractions were then concentrated and subjected to thin layer chromatography screening and the fractions with a satisfactory resolution of compounds were rechromatographed over silica gel to isolate the pure compounds. RESULTS: Four new furanoid diterpenes of clerodane types, Crispene A, B, C, and D (1-4), including one known furanoid diterpene glucoside, borapetoside E (5), were isolated from the stems of T. crispa. The structures of these compounds were elucidated by means of extensive spectroscopic analysis and by comparison of their spectral data with closely related compounds. CONCLUSION: We have reported four new furanoid diterpenes of clerodane types, including one known furanoid diterpene glucoside. This is the first report of any clerodane diterpene having olefinic bond between C-6 and C-7. SUMMARY: Crispene A, B, C, and D, four new furanoid diterpenes of clerodane types from Tinospora crispaCrispene C, an unusual furanoid diterpene with olifinic bond between C-6 and C-7First report of Crispene D as a free aglycone, though it was earlier reported as an enzymatic hydrolysis product. Abbreviation used: TLC: Thin layer chromatography, NMR: Nuclear magnetic resonance, COSY: Correlation spectroscopy, NOE: Nuclear overhauser effect, HPLC: High-performance liquid chromatography, ESI-MS: Electrospray ionization mass spectroscopy.

Targeting protein arginine N-methyltransferases with peptide-based inhibitors: opportunities and challenges.

Recently peptide-based inhibitors have been used to selectively inhibit a family of epigenetic enzymes called protein arginine N-methyltransferases (PRMTs), which has been implicated in different physiological processes and human diseases, such as heart disease and cancer. The diverse efforts to tease out subtle structural differences among PRMT enzymes in order to generate selective inhibitors as well as existing challenges in the field will be examined. The acquisition of PRMT substrate sequence preferences and structural information obtained from small-molecule inhibitors have helped in developing different peptide-based inhibitors that show great promise not only as inhibitors, but also as molecular probes to characterize PRMTs.

Arsenosugar induced blood and brain oxidative stress, DNA damage and neurobehavioral impairments.

The effect of Arsenosugar on motor function and contextual memory-related to place and event; the extent of DNA damage and oxidative stress in male swiss albino mice was investigated. Passive avoidance test was used for memory test; rota motor test was used for motor function. Several biochemical parameters were used for assessing oxidative stress due to arsenosugar ingestion. Decreased passive avoidance time and decreased retention time in rotating rod indicated disruption of normal neurobehavior. Significant dose-dependent DNA damage was found in mice blood and brain. Decreased super oxide dismutase, increased lipid peroxidation, decreased protein sulfohydryl content, increased protein carbonyl content in blood and hippocampal tissue; glutathione in blood and glutathione peroxidase in hippocampal tissue indicated the ability of arsenosugar to cause oxidative stress. This study concludes with evidence that arsenosugar ingestion causes higher oxidative stress, increases DNA damage in the blood and hippocampus in vivo. This might be responsible for the dysfunction of cognitive and motor functions. However, further investigation is suggested for deciphering the biomolecular mechanism.

Development and validation of a simple UV spectrophotometric method for the determination of levofloxacin both in bulk and marketed dosage formulations.

A rapid, specific and economic UV spectrophotometric method has been developed using a solvent composed of water:methanol:acetonitrile (9:0.5:0.5) to determine the levofloxacin content in bulk and pharmaceutical dosage formulations. At a pre-determined λmax of 292 nm, it was proved linear in the range of 1.0-12.0 µg/mL, and exhibited good correlation coefficient (R2=0.9998) and excellent mean recovery (99.00-100.07%). This method was successfully applied to the determination of levofloxacin content in five marketed brands from Bangladesh and the results were in good agreement with the label claims. The method was validated statistically and by recovery studies for linearity, precision, repeatability, and reproducibility. The obtained results proved that the method can be employed for the routine analysis of levofloxacin in bulks as well as in the commercial formulations.