Argentatin C Analogues with Potential Antinociceptive Activity and Other Triterpenoid Constituents from the Aerial Parts of Parthenium incanum

Ya-Ming Xu; E M Kithsiri Wijeratne; Aida Calderon-Rivera; Santiago Loya-López; Samantha Perez-Miller; Rajesh Khanna; A A Leslie Gunatilaka

doi:10.1021/acsomega.3c02302

Argentatin C Analogues with Potential Antinociceptive Activity and Other Triterpenoid Constituents from the Aerial Parts of Parthenium incanum

ACS Omega. 2023 May 25;8(22):20085-20095. doi: 10.1021/acsomega.3c02302. eCollection 2023 Jun 6.

Authors

Ya-Ming Xu¹, E M Kithsiri Wijeratne¹, Aida Calderon-Rivera², Santiago Loya-López², Samantha Perez-Miller², Rajesh Khanna^{2

3}, A A Leslie Gunatilaka¹

Affiliations

¹ Southwest Center for Natural Products Research, School of Natural Resources and the Environment, College of Agriculture and Life Sciences, University of Arizona, 1064 E. Lowell St., Tucson, Arizona 85719, United States.
² NYU Pain Research Center and Department of Molecular Pathobiology, College of Dentistry, New York University, 433 First Avenue, New York, New York 10010, United States.
³ Department of Neuroscience and Physiology and Neuroscience Institute, School of Medicine, New York University, New York, New York 10010, United States.

Abstract

Four new triterpenes, 25-dehydroxy-25-methoxyargentatin C (1), 20S-hydroxyargentatin C (2), 20S-hydroxyisoargentatin C (3), and 24-epi-argentatin C (4), together with 10 known triterpenes (5-14) were isolated from the aerial parts of Parthenium incanum. The structures of 1-4 were elucidated by detailed analysis of their spectroscopic data, and the known compounds 5-14 were identified by comparison of their spectroscopic data with those reported. Since argentatin C (11) was found to exhibit antinociceptive activity by decreasing the excitability of rat and macaque dorsal root ganglia (DRG) neurons, 11 and its new analogues 1-4 were evaluated for their ability to decrease the excitability of rat DRG neurons. Of the argentatin C analogues tested, 25-dehydroxy-25-methoxyargentatin C (1) and 24-epi-argentatin C (4) decreased neuronal excitability in a manner comparable to 11. Preliminary structure-activity relationships for the action potential-reducing effects of argentatin C (11) and its analogues 1-4, and their predicted binding sites in pain-relevant voltage-gated sodium and calcium channels (VGSCs and VGCCs) in DRG neurons are presented.