Synthesis of a series of novel dihydroartemisinin monomers and dimers containing chalcone as a linker and their anticancer activity.

A new series of monomer and dimer derivatives of dihydroartemisinin (DHA) containing substituted chalcones as a linker were synthesized and investigated for their cytotoxicity in human cancer cell lines HL-60 (leukemia), Mia PaCa-2 (pancreatic cancer), PC-3 (prostate cancer), LS180 (colon cancer) and HEPG2 (hepatocellular carcinoma). Some of these derivatives have greater antiproliferative and cytotoxic effects in tested cell lines than parent compound DHA. The structures of the all compounds were confirmed by IR, (1)H NMR and mass spectral data. Among the new derivatives, compounds 8, 14, 15, 20 and 24 were found to be more active than parent DHA against tested human cancer cell lines. DHA derivatives were found to be most active in human leukemia cell lines with compounds 8, 14, 15, 20 and 24 showed IC50 values less than 1 µM for 48 h whereas DHA has IC50 value of 2 µM at same time period. The most potent compounds 8 with IC50 = 0.3 µM (at par with doxorubicin (IC50 = 0.3 µM)) and 15 with IC50 = 0.4 µM, of the series, six and three times active than DHA (with IC50 = 2 µM) respectively were selected for further mechanistic work in human leukemia HL-60 cells.

Reverse-phase HPLC method for the quantification of two antihyperglycemic glycolipids in Oplismenus burmannii.

Glycolipids and sphingolipids are well known for their diverse biological activities like anticancer, anti-inflammatory, antistress, anti-HIV, hepatoprotective and antimicrobial. The present study deals with the activity-guided isolation and characterization of two antihyperglycemic glycolipids, (2S)-1,2-di-O-octadecanoyl-3-O-[α-d-galctopyranosyl-(1'' → 6')-O-ß-d-galactopyranosyl] glycerol (1) and 1-O-ß-d-glucopyranosyl-(2S,3S,4R,8E)-2-[(2R)-2-hydroxy-tetracosanoylamino]-2,3,4-octadecanetriol-8-ene (2) from Oplismenus burmannii and the development of a simple and validated reverse-phase HPLC analytical method for their quantification in the methanolic extracts of O. burmannii. The marker compounds 1 and 2 were isolated from the methanolic extract of O. burmannii and characterized on the basis of their spectroscopic data. Their antihyperglycemic potential was evaluated by determining their glucose uptake-stimulating potential in L6-GLUT4myc myotube cells. Finally, these analytes were separated on a Waters Spherisorb ODS 2 column with a binary gradient of methanol and water at a constant flow rate of 0.8 mL/min and detected using a photodiode array detector at 230 nm. The calibration curve was linear (r(2) > 0.999) over 1.2 orders of magnitude with acceptable accuracy, reproducibility and recovery (98.16-100.50%). The limits of detection and quantification for 1 and 2 were 1.36, 4.11 and 1.11, 3.35 µg/mL respectively. The method is simple, accurate, precise and selective and may be routinely used for the quality control analysis of whole plant extract of O. burmannii for these two glycolipids.

In vivo anti-diabetic activity of derivatives of isoliquiritigenin and liquiritigenin.

Isoliquiritigenin (ISL), a chalcone and liquiritigenin (LTG), a flavonoid found in licorice roots and several other plants. ISL displays antioxidant, anti-inflammatory, antitumor and hepatoprotective activities whereas LTG is an estrogenic compound, acts as an agonist selective for the ß-subtype of the oestrogen receptor. Both the phenolics were isolated from the rhizomes of Glycyrrhiza glabra. Five derivatives from ISL and four derivatives from LTG were synthesized. All the compounds were established by extensive spectroscopic analyses and screened through oral glucose tolerance test to gain preliminary information regarding the antihyperglycemic effect in normal Swiss albino male mice. ISL (1), ISL derivatives 3, 4, 5, 7 and LTG derivatives 9 and 10 showed significant blood glucose lowering effect. The structure-activity relationship indicated that the presence of ether and ester groups in ISL and LTG analogues are important for exhibiting the activity. Compounds 1, 4 and 10 were selected for in vivo antidiabetic activity and found to be potential candidates for treatment of diabetes. It is the first report on antidiabetic activity of ISL derivative 4 and LTG derivative 10.