Azaphilones from an Endophytic Penicillium sp. Prevent Neuronal Cell Death via Inhibition of MAPKs and Reduction of Bax/Bcl-2 Ratio > REFERENCE LIBRARY

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[EZ-Cytox] Azaphilones from an Endophytic Penicillium sp. Prevent Neuronal Cell Death via Inhibition of MAPKs a…

김상진
2022-01-28 09:15 625 1

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년도
2021
제품명
EZ-Cytox
학술지명
JOURNAL OF NATURAL PRODUCTS

Fourteen azaphilone-type polyketides (114), including nine new ones (16 and 810), were isolated from cultures of Vitex rotundifolia-associated Penicillium sp. JVF17, and their structures were determined by spectroscopic analysis together with computational methods and chemical reactions. Neuroprotective effects of the isolated compounds were evaluated against glutamate-induced neurotoxicity. Treatment with compounds 367, and 1114 increased cell viabilities of hippocampal neuronal cells damaged by glutamate, with compound 12 being the most potent. Compound 12 markedly decreased intracellular Ca2+ and nuclear condensation levels. Mechanistically, molecular markers of apoptosis induced by treatment with glutamate, i.e., phosphorylation of MAPKs and elevated Bax/Bcl-2 expression ratio, were significantly lowered by compound 12. The azaphilones with an isoquinoline core structure were more active than those with pyranoquinones, but N-substitution decreased the activity. This study, including the structure–activity relationship, indicates that the azaphilone scaffold is a promising lead toward the development of novel neuroprotective agents.

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김상진
2022-01-28 09:15
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