Azaphilones from an Endophytic Penicillium sp. Prevent Neuronal Cell Death via Inhibition of MAPKs and Reduction of Bax/Bcl-2 Ratio
- Authors
- Bang, Sunghee; Baek, Ji Yun; Kim, Geum Jin; Kim, Jaekyeong; Kim, SungJin; Deyrup, S.T.; Choi, Hyukjae; Kang, Ki Sung; Shim, Sang Hee
- Issue Date
- 27-Aug-2021
- Publisher
- American Chemical Society
- Citation
- Journal of Natural Products, v.84, no.8, pp.2226 - 2237
- Journal Title
- Journal of Natural Products
- Volume
- 84
- Number
- 8
- Start Page
- 2226
- End Page
- 2237
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/82107
- DOI
- 10.1021/acs.jnatprod.1c00298
- ISSN
- 0163-3864
- Abstract
- Fourteen azaphilone-type polyketides (1-14), including nine new ones (1-6 and 8-10), 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 3, 6, 7, and 11-14 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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