Paratrimerins J–Y, Dimeric Coumarins Isolated from the Stems of Paramignya trimera

• Published in: Journal of natural products (Washington, D.C.) Vol. 84; no. 2; pp. 310 - 326
• Main Authors: Quan, Khong Trong, Park, Hyun Bong, Yuk, Hanna, Lee, Seung Jin, Na, MinKyun
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society and American Society of Pharmacognosy 26-02-2021
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.0c00978

Paratrimerins J–Y (1–13 and 16–18), new dimeric coumarins, were obtained from the EtOH­(aq) extract of the stems of Paramignya trimera (Rutaceae) utilizing LC/MS guided isolation. The structures of the dimeric coumarins were elucidated based on 1D/2D NMR spectroscopic and HR-ESIMS data analyses. The absolute configurations of paratrimerins J–Y along with those of two known dimers paratrimerins A (14) and B (15) were established on the basis of the experimental and simulated ECD data. In addition, the absolute configurations of the sugar units of paratrimerins A, B, and J–V (1–15) were confirmed by LC/MS analysis on l-cysteine methyl ester and phenyl isothiocyanate derivatives. The variety of the absolute configurations of the dimeric diastereomers 1–15 highlighted a diversity in stereochemical outcomes following a Diels–Alder biosynthesis in P. trimera. With regard to P. trimera being a recently emerging medicinal resource for liver cancer, the dimers 1–18 were evaluated for cytotoxicity against a wide panel of human cancer cell lines. Paratrimerin W (16) was cytotoxic toward Huh7 hepatocellular carcinoma, HT1080 fibrosarcoma, and HT29 colorectal cancer cells with IC50 values of 14.9, 18.4, and 22.5 μM, respectively.