Neuroprotective activity of N-substituted triterpenic azines synthesized from lupeol.

MUSSO, F.; ALZA, N.P.; SALVADOR, G.; FARAONI, M.B.

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias 2023; 2023

Currently, Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease, and its prevalence has doubled in the past 25 years. The main hallmark of PD is the progressive loss of dopaminergic neurons in the substantia nigra, which led to the typical motor symptoms. 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 azines in 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=N-N=C), interesting molecules for their biological properties. From the natural triterpene 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 through a microwave-assisted method, with good yield. Secondly, the neuroprotective activity of these compounds was evaluated in vitro. Neuroblastoma cells IMR-32 were exposed to non-cytotoxic concentrations of azines in the presence of 6-OHDA (25 µM), andcell viability was determined by the MTT assay. Variable efficiency in neuroprotection was observed between azine derivatives. Whereby all of them showed some degree of restoration of cell viabilityat 50 µM, only three compounds displayed strong defense against 6-OHDA neurotoxicity at 10 µM, reestablishing control levels. The more active azines have the structural features of being N-substituted with a para-metoxy or meta-metoxy benzene at position 31, or with a furane ring. To conclude, these azines obtained from 30-oxolupeol are potential neuroprotective agents against 6-OHDA neurotoxicity and could be an inspiration for the development of new drugs for PD treatment.