Realization of the Reversible Vesicle–Micelle Transition of Vitamin-Derived Bolaamphiphiles by Heat Change Monitoring

The real-time energetics involved in the structural change of a zwitterionic vitamin-derived bolaamphiphiles (DDO) vesicles, which were induced by conventional surfactants, such as hexadecyltrimethylammonium bromide (CTAB), sodium dodecyl sulfate (SDS), and Triton X-100 (TX100), was characterized by isothermal titration calorimetry (ITC). Interactions of both CTAB and SDS with DDO were accompanied with considerable heat release whereas the interaction energetics between TX-100 and the vesicles were small. However, the transition of DDO vesicles to micelles did occur upon the addition of all of the three surfactants. Fine inflection points were observed in heat flow enthalpograms, which indicated systematically the change of vesicle structure. By monitoring the interaction of CTAB with DDO, we found that heat release kept constant over a certain concentration range at higher temperatures. The repairing effect of heating was revealed and a reversible transition from micelles to vesicles of DDO was thus realized. Further encapsulation of fluorescein in DDO vesicles proved that the reversible vesicle–micelle transition was controllable. This research demonstrates that ITC combined with complementary analytical methods such as dynamic light scattering (DLS) and transmission electron microscopy (TEM) helps to get the real-time information of the structural changes of vesicles. It also shows that these synthetic novel bolaamphiphiles offer great promise for designing controllable release system

Straightforward synthesis, characterization, and cytotoxicity evaluation of hybrids of natural alkaloid evodiamine/rutaecarpine and thieno[2,3-<i>d</i>]pyrimidinones

Dozens of hybrids of natural alkaloid evodiamine/rutaecarpine and thieno[2,3-d]pyrimidinones were synthesized in a straightforward method by condensation of substituted 2H-thieno[2,3-d][1, 3]oxazine-2,4(1H)-diones or N-methyl-2H-thieno[2,3-d][1, 3]oxazine-2,4(1H)-dione with 3,4-dihydro-β-carbolines. In vitro cytotoxic assay discovered that compounds 9a, 10e, 11a, 11d, 11f, and 12a could induce antiproliferation against four different types of human cancer cells while compounds 10f and 12e were inactive. Notably, compound 11a displayed potent cell cytotoxicity for human non-small cell lung cancer cells A549, PC-9, human prostate cancer cells PC-3, and human breast cancer cell line MCF-7. Furthermore, compound 11a exhibited strong colony formation inhibition to A549 cells. These results unfold potential anticancer therapeutic applications of hybrids of thieno[2,3-d]pyrimidinones and quinazolinones.</p

Supplementary Data from Microdose-Induced Drug–DNA Adducts as Biomarkers of Chemotherapy Resistance in Humans and Mice

Chemical structures, patient data, mouse survival curves, additional biomarker data</p