LC-MS- and 1H NMR Spectroscopy-Guided Identification of Antifungal Diterpenoids from Sagittaria latifolia

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• 作者：Ranga Rao Ravu ; Melissa R. Jacob ; Cynthia Jeffries ; Ying Tu ; Shabana I. Khan ; Ameeta K. Agarwal ; R. Kiplin Guy ; Larry A. Walker ; Alice M. Clark ; Xing-Cong Li
• 刊名：Journal of Natural Products
• 出版年：2015
• 出版时间：September 25, 2015
• 年：2015
• 卷：78
• 期：9
• 页码：2255-2259
• 全文大小：296K
• ISSN：1520-6025

文摘

Antifungal screening of small-molecule natural product libraries showed that a column fraction (CF) derived from the plant extract of Sagittaria latifolia was active against the fungal pathogen Cryptococcus neoformans. Dereplication analysis by liquid chromatography鈥搈ass spectrometry (LC-MS) and proton nuclear magnetic resonance spectroscopy (p>1p>H NMR) indicated the presence of new compounds in this CF. Subsequent fractionation of the plant extract resulted in the identification of two new isopimaradiene-type diterpenoids, 1 and 2. The structures of 1 and 2 were determined by chemical methods and spectroscopic analysis as isopimara-7,15-dien-19-ol 19-O-伪-pan class="smallcaps">lpan>-arabinofuranoside and isopimara-7,15-dien-19-ol 19-O-伪-pan class="smallcaps">lpan>-(5鈥?acetoxy)arabinofuranoside, respectively. Compound 1 exhibited IC₅₀ values of 3.7 and 1.8 渭g/mL, respectively, against C. neoformans and C. gattii. Its aglycone, isopimara-7,15-dien-19-ol (3), resulting from acid hydrolysis of 1, was also active against the two fungal pathogens, with IC₅₀ values of 9.2 and 6.8 渭g/mL, respectively. This study demonstrates that utilization of the combined LC-MS and p>1p>H NMR analytical tools is an improved chemical screening approach for hit prioritization in natural product drug discovery.