skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Efficient discrimination of natural stereoisomers of chicoric acid, an HIV-1 integrase inhibitor

Abstract

Plants from the Asteraceae family are known to contain a wide spectrum of phytochemicals with various nutraceutical properties. One important phytochemical, chicoric acid (CA), is reported to exist in plants, such as Sonchus oleraceus and Bidens pilosa, as stereoisomers. They occur either as the naturally abundant RR-chicoric acid (RR-CA), or the less abundant RS-chicoric acid (RS-CA), also known as meso-chicoric acid. To date, little is known about the biological activity of RS-CA, but there is evidence of its anti-HIV (human immunodeficiency virus) properties. In this study, a reliable analytical method was developed to distinguish between the two stereoisomers detected in S. oleraceus and B. pilosa. Structure identification used liquid chromatography–mass spectrometry (LC-MS) in combination with ultraviolet radiation (UV) -induced geometrical isomerization, molecular dynamics (MD) simulations, and density functional theory (DFT) models. Optimized structures from DFT calculations were used for docking studies against the HIV-1 integrase enzyme. Different retention times on the reverse phase chromatograms revealed the plants produce two different CA stereoisomers: S. oleraceus produced the RR-CA isomer, while B. pilosa produced the RS-CA isomer. DFT results demonstrated the RR-CA molecule was more stable than RS-CA due to the stabilizing force of intra-molecular hydrogen bonding. Differences in the HIV-1 integrasemore » enzyme binding modes were observed, with the RR-CA being a more potent inhibitor than the RS-CA molecule. The results highlight the significance of plant metabolite structural complexity from both chemical and biological perspectives. Artificial formation of geometrical isomers, in combination with the predictive ability of DFT models and the resolving power of the LC-MS, can be exploited to distinguish closely related compounds, in particular stereoisomers.« less

Authors:
; ; ; ; ; ; ; ORCiD logo;
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1497012
Report Number(s):
PNNL-SA-137796
Journal ID: ISSN 1011-1344
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
Journal of Photochemistry and Photobiology B: Biology
Additional Journal Information:
Journal Volume: 189; Journal Issue: C; Journal ID: ISSN 1011-1344
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
chicoric acid, RR-chicoric acid, RS-chicoric acid, Sonchus oleraceus, bidens pilosa, LC-MS, DFT models, HIV-1 integrase

Citation Formats

Nobela, Ofentse, Renslow, Ryan S., Thomas, Dennis G., Colby, Sean M., Sitha, Sanyasi, Njobeh, Patrick Berka, du Preez, Louis, Tugizimana, Fidele, and Madala, Ntakadzeni Edwin. Efficient discrimination of natural stereoisomers of chicoric acid, an HIV-1 integrase inhibitor. United States: N. p., 2018. Web. doi:10.1016/j.jphotobiol.2018.10.025.
Nobela, Ofentse, Renslow, Ryan S., Thomas, Dennis G., Colby, Sean M., Sitha, Sanyasi, Njobeh, Patrick Berka, du Preez, Louis, Tugizimana, Fidele, & Madala, Ntakadzeni Edwin. Efficient discrimination of natural stereoisomers of chicoric acid, an HIV-1 integrase inhibitor. United States. doi:10.1016/j.jphotobiol.2018.10.025.
Nobela, Ofentse, Renslow, Ryan S., Thomas, Dennis G., Colby, Sean M., Sitha, Sanyasi, Njobeh, Patrick Berka, du Preez, Louis, Tugizimana, Fidele, and Madala, Ntakadzeni Edwin. Sat . "Efficient discrimination of natural stereoisomers of chicoric acid, an HIV-1 integrase inhibitor". United States. doi:10.1016/j.jphotobiol.2018.10.025.
@article{osti_1497012,
title = {Efficient discrimination of natural stereoisomers of chicoric acid, an HIV-1 integrase inhibitor},
author = {Nobela, Ofentse and Renslow, Ryan S. and Thomas, Dennis G. and Colby, Sean M. and Sitha, Sanyasi and Njobeh, Patrick Berka and du Preez, Louis and Tugizimana, Fidele and Madala, Ntakadzeni Edwin},
abstractNote = {Plants from the Asteraceae family are known to contain a wide spectrum of phytochemicals with various nutraceutical properties. One important phytochemical, chicoric acid (CA), is reported to exist in plants, such as Sonchus oleraceus and Bidens pilosa, as stereoisomers. They occur either as the naturally abundant RR-chicoric acid (RR-CA), or the less abundant RS-chicoric acid (RS-CA), also known as meso-chicoric acid. To date, little is known about the biological activity of RS-CA, but there is evidence of its anti-HIV (human immunodeficiency virus) properties. In this study, a reliable analytical method was developed to distinguish between the two stereoisomers detected in S. oleraceus and B. pilosa. Structure identification used liquid chromatography–mass spectrometry (LC-MS) in combination with ultraviolet radiation (UV) -induced geometrical isomerization, molecular dynamics (MD) simulations, and density functional theory (DFT) models. Optimized structures from DFT calculations were used for docking studies against the HIV-1 integrase enzyme. Different retention times on the reverse phase chromatograms revealed the plants produce two different CA stereoisomers: S. oleraceus produced the RR-CA isomer, while B. pilosa produced the RS-CA isomer. DFT results demonstrated the RR-CA molecule was more stable than RS-CA due to the stabilizing force of intra-molecular hydrogen bonding. Differences in the HIV-1 integrase enzyme binding modes were observed, with the RR-CA being a more potent inhibitor than the RS-CA molecule. The results highlight the significance of plant metabolite structural complexity from both chemical and biological perspectives. Artificial formation of geometrical isomers, in combination with the predictive ability of DFT models and the resolving power of the LC-MS, can be exploited to distinguish closely related compounds, in particular stereoisomers.},
doi = {10.1016/j.jphotobiol.2018.10.025},
journal = {Journal of Photochemistry and Photobiology B: Biology},
issn = {1011-1344},
number = C,
volume = 189,
place = {United States},
year = {2018},
month = {12}
}