Design, synthesis and biological evaluation of N-oxide derivatives with potent in vivo antileishmanial activity.

Leishmaniasis is a neglected disease that affects 12 million people living mainly in developing countries. Herein, 24 new N-oxide-containing compounds were synthesized followed by in vitro and in vivo evaluation of their antileishmanial activity. Compound 4f, a furoxan derivative, was particularly remarkable in this regard, with EC50 value of 3.6 µM against L. infantum amastigote forms and CC50 value superior to 500 µM against murine peritoneal macrophages. In vitro studies suggested that 4f may act by a dual effect, by releasing nitric oxide after biotransformation and by inhibiting cysteine protease CPB (IC50: 4.5 µM). In vivo studies using an acute model of infection showed that compound 4f at 7.7 mg/Kg reduced ~90% of parasite burden in the liver and spleen of L. infantum-infected BALB/c mice. Altogether, these outcomes highlight furoxan 4f as a promising compound for further evaluation as an antileishmanial agent.

Rutin inhibits the in vitro formation of advanced glycation products and protein oxidation more efficiently than quercetin

Introduction: The exacerbated generation of advanced glycation end products (AGEs) triggers the onset of diabetic complications associated with hyperglycemia. The search for natural bioactive compounds that can inhibit AGE formation has gained immense interest. Quercetin and its glycoside derivative, rutin, are powerful antioxidants. They have been studied due to their potential to mitigate the disturbances observed in diabetes; however, studies comparing their antiglycation effects are limited. The aim of the present study was to compare the in vitro antiglycation potentials of quercetin and rutin. Methods: The in vitro model system of protein glycation was applied using bovine serum albumin (10 mg/mL) incubated with glucose (0.5 M) in the absence or presence of aminoguanidine (1 mM, prototype anti-AGE agent), metformin (1 mM), quercetin (100, 50, or 12.5 µM), or rutin (100, 50, or 12.5 µM). Before initiating incubations (day 0) and after 10, 20, and 30 days, aliquots were assayed for fluorescent AGEs. Markers of amino acid oxidation (dityrosine, N'-formylkynurenine, kynurenine), protein carbonyl groups (PCO), and protein crosslink formation were assessed after 30 days. Results: Both quercetin and rutin inhibited the formation of AGEs and decreased the PCO levels in a concentration-dependent manner, and moreover, the effect of rutin was more prominent than that of quercetin. Quercetin and rutin also decreased the formation of amino acid oxidation products and protein crosslinks; the best effects were observed in incubations with rutin. Conclusion: Rutin exhibited the most potent antiglycation and antioxidant activities, which may be attributed to the minor occurrence of interactions between albumin and rutin, making rutinnoside more available to exert its effects.