Anti-inflammatory+Antfifungal Effects of N-glutaroyl and N-succinyl Melatonin

Objectives: To modify melatonin with glutaroyl/succinyl groups and to investigate their anti-inflammatory and antifungal properties.
Methods: N-glutaroyl or N-succinyl melatonin were synthesized by combining melatonin with either glutaroyl or succinyl group, in the presence of dicyclohexylcarbodiimide. They were purified by column chromatography, identified by proton nuclear magnetic resonance spectroscopy. Candida albicans ATCC MYA-2876 both in planktonic and biofilm form was treated with either derivative at final concentrations 500-4,000 μM for 24 h (37 ° C) using 1-64 μM nystatin as a positive control. Candidal growth was investigated with a microplate reader. Regarding anti-inflammation, 1x10⁵ cells/well of RAW 264.7 cells were activated by 1 mg/ml lipopolysaccharides for 24 h in RPMI medium in the presence of testing substances at the final concentrations of 125-2,000 mM. Nitric oxide (NO), tumor necrosis factor alpha (TNF-α) amount was examined by Griess test and ELISA assay, respectively.
Results: Both derivatives reduced planktonic fungal cells in a dose-dependent manner, and 4,000 μM of each derivative could inhibit C. albicans. approximately equal to 1 μM of nystatin, but they could not exert fungal growth inhibition in biofilm form. Regarding anti-inflammatory effect, they inhibited NO in a dose-dependent manner but not reduced the quantity of TNF-α that was similar to the melatonin.
Conclusions: N-glutaroyl and N-succinyl melatonin exhibited the anti-inflammatory ability via NO reducing mechanism and the antifungal ability of planktonic C. albicans.