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Glycation of proteins is believed to be involved in the pathogenesis of diabetic complications, and thus the development of potent inhibitors of protein glycation is highly desirable. We tested the inhibitory effects of 12 hydrazide compounds against protein glycation and compared them with the effects of aminoguanidine (AG), a well-known inhibitor. When bovine serum albumin (BSA) was incubated with 100 mmol/l mannose for 10 days at 37 °C in the presence and absence of hydrazide compounds or AG at 1 mmol/l, only p-anisic hydrazide inhibited Amadori product formation. On the other hand, 8 hydrazides as well as AG inhibited the formation of advanced glycation end products (AGEs). 8-Quinolinecarboxylic hydrazide (8-QCH), the most potent hydrazide, was more effective than AG. Neither 8-QCH nor AG affected the spontaneous decrease in Amadori products of preglycated BSA in the absence of sugar, but suppressed the spontaneous increase in AGEs from preglycated BSA, with higher potency of 8-QCH relative to AG. The results indicate that 8-QCH is a more potent inhibitor of AGE formation than AG and suggest that the inhibition mechanisms of 8-QCH and AG resemble each other.

Naphtho[2,[1,5]naphthyridine 7,11 -dioxide was prepared and deoxygenation of the N-oxide groups with carbon disulfide^SJ was reported. Of the two N-oxide groups, the 11 -oxide was reduced with a 32% yield, whereas the 7-oxide remained unreacted. Molecular orbital calculations were then applied to rationalize the regioselectivity of CS 2 reduction of the known heteroaromatic N-oxides. The calculation result revealed that the electrophilic attack of CS 2 on the oxygen atom initiates the reaction. Subsequently, the reaction proceeds via a cyclic intermediate. When more than one intermediate is possible, the reaction through the more stable intermediate is preferred. Brought to you by | University of Arizona Authenticated Download Date | 5/28/15 9:41 PM Vol. 2, No. 5, 1996 Reduction of heteroaroniatic N-oxides with carbon ExperimentalMelting points were taken using a Yanagimoto micro-melting point hot-stage apparatus and are uncorrected. Ή NMR spectra were recorded with a JEOL JMN GX-270 spectrometer at 270 MHz with tetramethylsilane fTMS) as the internal standard. Chemical shifts are given on the δ scale (ppm). The following abbreviations are used: s=singlet,