Neuroprotective activity of N-substituted triterpenic azines synthesized from lupeol

FLORENCIA MUSSO; NATALIA ALZA; GABRIELA SALVADOR; MARÍA BELÉN FARAONI

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias; 2023

Currently, Parkinson´s disease (PD) is the second most commonneurodegenerative disorder after Alzheimer´s disease, and its prevalence hasdoubled in the past 25 years. The main hallmark of PD is the progressive loss ofdopaminergic neurons in the substantia nigra, which led to the typical motorsymptoms. Despite decades of intensive efforts in finding a cure for PD,treatments alleviate symptoms through restoring dopamine deficiency or surgery.Our aim was to test the potential neuroprotection of a series of triterpenic azinesin a cellular model of PD using the neurotoxic 6-hydroxydopamine (6-OHDA).Firstly, a semisynthetic approach was used to obtain a series of azines (C=NN=C), interesting molecules for their biological properties. From the naturaltriterpene lupeol isolated from the plant Chuquiraga erinacea, we prepared 30-oxolupeol by allylic oxidation, being this latter the template for azine synthesis.Combining 30-oxolupeol different aromatic hydrazones led to 16 azines througha microwave-assisted method, with good yield. Secondly, the neuroprotectiveactivity of these compounds was evaluated in vitro. Neuroblastoma cells IMR-32were exposed to non-cytotoxic concentrations of azines in the presence of 6-OHDA (25 µM), and cell viability was determined by the MTT assay. Variableefficiency in neuroprotection was observed between azine derivatives. Wherebyall of them showed some degree of restoration of cell viability at 50 µM, only threecompounds displayed strong defense against 6-OHDA neurotoxicity at 10 µM,reestablishing control levels. The more active azines have the structural featuresof being N-substituted with a para-metoxy or meta-metoxy benzene at position31, or with a furane ring. To conclude, these azines obtained from 30-oxolupeolare potential neuroprotective agents against 6-OHDA neurotoxicity and could bean inspiration for the development of new drugs for PD treatment.