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

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2015-09, Vol.78 (9), p.2255-2259
• Main Authors: Ravu, Ranga Rao, Jacob, Melissa R, Jeffries, Cynthia, Tu, Ying, Khan, Shabana I, Agarwal, Ameeta K, Guy, RKiplin, Walker, Larry A, Clark, Alice M, Li, Xing-Cong
• Format: Article
• Language: English
• Subjects: Cryptococcus neoformans; Sagittaria latifolia
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.5b00470

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-mass spectrometry (LC-MS) and proton nuclear magnetic resonance spectroscopy ( super(1)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- alpha -l-arabinofuranoside and isopimara-7,15-dien-19-ol 19-O- alpha -l-(5'-acetoxy)arabinofuranoside, respectively. Compound 1 exhibited IC sub(50) values of 3.7 and 1.8 mu 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 IC sub(50) values of 9.2 and 6.8 mu g/mL, respectively. This study demonstrates that utilization of the combined LC-MS and super(1)H NMR analytical tools is an improved chemical screening approach for hit prioritization in natural product drug discovery.