Anti-inflammatory Activity of Piperlotines
DOI:
https://doi.org/10.29356/jmcs.v64i3.1152Keywords:
Mechanochemistry, piper amides, inflammation, tuberculosisAbstract
Abstract. In the present study we evaluated six α,β-unsaturated amides named piperlotines (for being isolated originally from Piper species) as new in vivo anti-inflammatory agents. In addition, we report the mechanosynthesis of two of them by mechanochemical activation of a Horner-Wadsworth-Emmons reaction. The reaction of β-amidophosphonate 4, an aromatic aldehyde and K2CO3 under grinding in a mortar and pestle afforded piperlotines 5-6 in good yields (70-88%) in short reaction times, obtaining only (E)-diastereomer. Piperlotines previously prepared were tested as anti-inflammatory and antibacterial agents. In this respect, derivatives 2 and 6 exhibited excellent in vivo anti-inflammatory activity on mice, especially trough topical administration (TPA acute inflammation model). Furthermore, piperlotine A, and compounds 2 and 6 had slight antimycobacterial activity against Mycobacterium tuberculosis (MIC = 50 µg/mL). In conclusion, the solvent-free mechanosynthesis of piperlotines produced valuable compounds that could serve as templates for further investigation in the search of better drug-like compounds for the treatment of inflammatory diseases.
Resumen. En la presente investigación se evaluó la actividad anti-inflamatoria in vivo de seis amidas α,β-insaturadas, identificadas en la literatura como piperlotinas debido a su inicial aislamiento a partir de especies vegetales del género Piper (como las pimientas). La reacción del β-amidofosfonato 4 con un aldehído aromático y K2CO3 en molienda con mortero y pistilo produjo las piperlotinas 5-6 con buenos rendimientos (70-80%) en tiempos cortos de reacción, obteniendo solamente el diastereoisómero (E). Las piperlotinas preparadas se evaluaron como agentes anti-inflamatorios y antibacterianos, observando excelente actividad anti-inflamatoria para los derivados 2 y 6, especialmente cuando se probaron mediante administración tópica (modelo de inflamación aguda por TPA). Además, la piperlotina A y los derivados 2 y 6 mostraron actividad antibacteriana contra Mycobacterium tuberculosis (MIC = 50 µg/mL). En conclusión, la síntesis de piperlotinas a través de molienda en condiciones libres de disolvente generó importantes productos que pueden ser utilizados como punto de partida para generar nuevos compuestos bioactivos para el tratamiento de padecimientos relacionados con la inflamación.
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