Synthesis of novel lipophilic N-substituted norcantharimide derivatives and evaluation of their anticancer activities.

This research attempted to study the effect of lipophilicity on the anticancer activity of N-substituted norcantharimide derivatives. Twenty-three compounds were synthesized and their cytotoxicities against five human cancer cell lines studied. The lipophilicity of each derivative was altered by its substituent, an alkyl, alkyloxy, terpenyl or terpenyloxy group at the N-position of norcantharimide. Further, among all synthesized derivatives studied, the compounds N-farnesyloxy-7-oxabicyclo[2.2.1]heptane-2,3-dicarboximide (9), and N-farnesyl-7-oxabicyclo[2.2.1]heptane-2,3-dicarboximide (18), have shown the highest cytotoxicity, anti-proliferative and apoptotic effect against human liver carcinoma HepG2 cell lines, yet displayed no significant cytotoxic effect on normal murine embryonic liver BNL CL.2 cells. Their overall performance led us to believe that these two compounds might be potential candidates for anticancer drugs development.

Synthesis and anticancer activity of a novel series of 9-O-substituted berberine derivatives: a lipophilic substitute role.

To alter its hydrophobicity, a series of compounds bearing 9-O-alkyl- or 9-O-terpenyl- substituted berberine were synthesized and evaluated for anticancer activity against human cancer HepG2 and HT29 cell lines. We found that the lipophilic substitute of 9-O-alkyl- and 9-O-terpenyl berberine derivatives plays a role in inhibiting the human cancer cell growth and its activity could be maximized with the optimized substitute type and chain length. Most strikingly, nonetheless, of the six compounds prepared, sample 8, a farnesyl 9-O-substituted berberine, showed either comparable or better cytotoxic activity against human cancer HepG2 cell line than that of berberine. Compound 8 had also shown a 104-fold antiproliferation activity in compare with berberine against human hepatoma HepG2 cell lines after 48 incubation hours. Further, in Hoechst 33258 and annexin V-FITC/PI staining analyses it induced apoptosis in HepG2 cells at lower concentration than that of berberine for 24h. Take all; farnesyl 9-O-substituted berberine could be a potential candidate for new anticancer drug development.

A novel method for estimating the focal size of two confocal high-intensity focused ultrasound transducers.

Estimating the focal size and position of a high-intensity focused ultrasound (HIFU) transducer remains a challenge since traditional methods, such as hydrophone scanning or schlieren imaging, cannot tolerate high pressures, are directional, or provide low resolution. The difficulties increase when dealing with the complex beam pattern of a multielement HIFU transducer array, e.g., two transducers facing each other. In the present study we show a novel approach to the visualization of the HIFU focus by using shockwave-generated bubbles and a diagnostic B-mode scanner. Bubbles were generated and pushed by shock waves toward the HIFU beam, and were trapped in its pressure valleys. These trapped bubbles moved along the pressure valleys and thereby delineated the shape and size of the HIFU beam. The main and sidelobes of 1.1- and 3.5 MHz HIFU beams were clearly visible, and could be measured with a millimeter resolution. The combined foci could also be visualized by observing the generation of sustained inertial cavitation and enhanced scattering. The results of this study further demonstrate the possibility of reducing the inertial cavitation threshold by the local introduction of shock wave-generated bubbles, which might be useful when bubble generation and cavitation-related bioeffects are intended within a small region in vivo.