Sarah Mazzotta1,2, Luca Frattaruolo1, Matteo Brindisi1, Cristina Ulivieri3, Francesca Vanni3, Antonella Brizzi4, Gabriele Carullo1, Anna R Cappello1, Francesca Aiello1. 1. Department of Pharmacy, Health & Nutritional Sciences2, University of Calabria, 87036 Arcavacata di Rende (CS), Italy. 2. Department of Organic & Medicinal Chemistry, University of Seville, n. 2, 41012 Seville, Spain. 3. Department of Life Sciences, University of Siena, Via Aldo Moro, n. 2, 53100 Siena, Italy. 4. Department of Biotechnology, Chemistry & Pharmacy, University of Siena, Via Aldo Moro, n. 2, 53100 Siena, Italy.
Abstract
Aim: Over the years, indole has proved to be a versatile scaffold for the design of molecules acting as anti-inflammatory agents. Materials & Methods: A small library of 3-amino-alkylated indoles has been obtained by an optimized Mannich green approach. The anti-inflammatory activity of the new 3-amino-alkylated indoles, GLYC 0-10, was evaluated in RAW 264.7 macrophages. Results: The anti-inflammatory activity of the new 3-amino-alkylated indoles, GLYC 0-10, was evaluatedn and, among them, GLYC 4, 5 and 9 displayed the greatest inhibitory effects on nitric oxide production, with IC50 values of 5.41, 4.22 and 6.3 μM, respectively. Conclusion: Our outcomes, overall, highlight the importance of the indole substitution in the anti-inflammatory activity of these compounds, exerted by acting on the interlinked NF-κB/ERK1/2 pathways.
Aim: Over the years, indole has proved to be a versatile scaffold for the design of molecules acting as anti-inflammatory agents. Materials & Methods: A small library of 3-amino-alkylated indoles has been obtained by an optimized Mannich green approach. The anti-inflammatory activity of the new 3-amino-alkylated indoles, GLYC 0-10, was evaluated in RAW 264.7 macrophages. Results: The anti-inflammatory activity of the new 3-amino-alkylated indoles, GLYC 0-10, was evaluatedn and, among them, GLYC 4, 5 and 9 displayed the greatest inhibitory effects on nitric oxide production, with IC50 values of 5.41, 4.22 and 6.3 μM, respectively. Conclusion: Our outcomes, overall, highlight the importance of the indole substitution in the anti-inflammatory activity of these compounds, exerted by acting on the interlinked NF-κB/ERK1/2 pathways.
Authors: Gabriele Carullo; Fabio Sciubba; Paolo Governa; Sarah Mazzotta; Luca Frattaruolo; Giorgio Grillo; Anna Rita Cappello; Giancarlo Cravotto; Maria Enrica Di Cocco; Francesca Aiello Journal: Pharmaceuticals (Basel) Date: 2020-05-14