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Open AccessArticle

Synthesis of Novel Baicalein Amino Acid Derivatives and Biological Evaluation as Neuroprotective Agents

1
School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China
2
Beijing Shijingshan District Medical Security Bureau, 66 Yangzhuang Road, Shijingshan, Beijing 100043, China
3
Fuxin Health School, Liaoning 123000, China
*
Authors to whom correspondence should be addressed.
Molecules 2019, 24(20), 3647; https://doi.org/10.3390/molecules24203647
Received: 28 August 2019 / Revised: 27 September 2019 / Accepted: 3 October 2019 / Published: 9 October 2019
Baicalein, a famously effective component of the traditional Chinese medicine Rhizoma Huang Qin (Scutellaria altissima L.), has been proved to have potent neuroprotection and anti-platelet aggregation effects with few side effects. Meanwhile, recent studies have revealed that the introduction of amino acid to baicalein could improve its neuroprotective activity. In the present study, a series of novel baicalein amino acid derivatives were designed, synthesized, and screened for their neuroprotective effect against tert-butyl, hydroperoxide-induced, SH-SY5Y neurotoxicity cells and toxicity on the normal H9C2 cell line by standard methylthiazol tetrazolium (MTT) assay. In addition, all of the newly synthesized compounds were characterized by 1H-NMR, 13C-NMR, and high resolution mass spectrometry (HR-MS). The results showed that most of the compounds provided more potent neuroprotection than baicalein, and were equivalent to the positive drug edaravin. They showed no obvious cytotoxicity on normal H9C2 cells. Notably, the most active compound 8 displayed the highest protective effect (50% effective concentration (EC50) = 4.31 μM) against tert-butyl, hydroperoxide-induced, SH-SY5Y neurotoxicity cells, which was much better than the baicalein (EC50 = 24.77 μM) and edaravin (EC50 = 5.62 μM). Further research on the chick chorioallantoic membrane (CAM) model indicated that compound 8 could significantly increase angiogenesis, which might promote neurovascular proliferation. The detection of apoptosis analysis showed that compound 8 could dramatically alleviate morphological manifestations of cell damage. Moreover, the benzyloxycarbonyl (cbz)-protected baicalein amino acid derivatives showed better neuroprotective activity than the t-Butyloxy carbonyl (boc)-protected derivatives. View Full-Text
Keywords: baicalein; neuroprotective effect; amino acids derivatives; SH-SY5Y cell; chick chorioallantoic membrane baicalein; neuroprotective effect; amino acids derivatives; SH-SY5Y cell; chick chorioallantoic membrane
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MDPI and ACS Style

Jia, X.; Jia, M.; Yang, Y.; Wang, D.; Zhou, F.; Zhang, W.; Huang, X.; Guo, W.; Cai, D.; Chen, H.; Qi, J.; Zhou, S.; Ren, H.; Xu, B.; Ma, T.; Wang, P.; Lei, H. Synthesis of Novel Baicalein Amino Acid Derivatives and Biological Evaluation as Neuroprotective Agents. Molecules 2019, 24, 3647.

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