Natural products embedded crown ethers as potent insulin secretory agents.

Natural products embedded crown ethers were prepared by utilizing bioactive natural products including chrysin, tetrahydroisoquinoline (THIQ), and biochanin-A. The prepared crown ether scaffolds were evaluated and compared with their natural product precursors for insulin secretory activity on isolated mice islets and for their fluorescent properties. All the crown adducts were found more active as compared to their natural product precursors. Bischrysin 32-crown-10 (6d), THIQ 15-Crown-5 (6a) and chrysin 16-crown-5 (6c) showed mild, moderate and strong insulin secretory activity, respectively when compared with the standard drug tolbutamide (TB). Particularly crown derivative 6c showed strong activity (31.10 ng/islet/h) that is almost two (02) fold higher than that of standard drug TB (16.82 ng/islet/h). To the best of our knowledge crown ethers based antidiabetic study is being reported for the first time in literature through this work. Furthermore, fluorescence study showed the significant increase in absorption and emission maximum (hypsochromic effect) in crown structures when compared with their natural product precursors. Present optimistic results obtained from this study may be a guided template for developing new effective insulin secretory agents.

Newly synthesized tetraoxa-diaza crown ether derivatives versus commercialized crown ethers in the separation of positional isomers with capillary electrophoresis.

Three new tetraoxa-diaza derivatives of 1,4,10,13-tetraoxa-7,16-diazacyclo-octadecane (R-1, R-2 and R-3) and three commercially available crown ethers, 18-crown-6 (18C6), (+)-18-crown-6-tetracarboxilic acid (18C6H4) and 1,4,10,13-tetraoxa-7,16-diazacyclo-octadecane, were investigated to separate the positional isomers of aminophenol, aminobenzoic acid and aminocresol. The running electrolyte, in which the crown ethers were dissolved, was a 50 mM Tris solution adjusted to pH 2.0 with hydrochloric acid. Using 50 mM H3PO4 buffer, whose pH was adjusted to 2.0 with Tris, or only hydrochloric acid solution with the same pH, did not allow good separations for the tested components. The effect of the crown ether concentration on the separation of the 11 positional isomers was studied in the concentration range of 10-50 mM. The best separations were achieved using the 18C6 and the 18C6H4 crown ethers: 9 isomers out of 11 could be separated within one run. The m- and p-aminophenol isomers could not be separated under the investigated experimental conditions. The newly synthesized tetraoxa-diaza crown ether derivatives were only found suitable for the separation of aminobenzoic acid positional isomers. The macrocyclic ring of the tetraoxa-diaza crown ethers was not able to form a stable inclusion complex with the tested positional isomers. Consequently, the aminophenol and aminocresol isomers were not separated, the isomers migrated with the same or very similar velocities.