Five new 2-(2-phenylethyl)chromone derivatives from agarwood

• Published in: Journal of natural medicines Vol. 74; no. 3; pp. 561 - 570
• Main Authors: Shibata, Shunsuke, Sugiyama, Takuji, Uekusa, Yoshinori, Masui, Ryo, Narukawa, Yuji, Kiuchi, Fumiyuki
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.06.2020; Springer Nature B.V
• Subjects: Biological products; Biomedical and Life Sciences; Biomedicine; Chemical compounds; Circular dichroism; Complementary & Alternative Medicine; Fluorescence polarization; Incense; Inhibitor drugs; Medicinal Chemistry; NMR; Nuclear magnetic resonance; Original Paper; Pharmacology/Toxicology; Pharmacy; Phosphodiesterase; Plant Sciences; Spectroscopy; Phosphodiesterase inhibitor; Agarwood; 2-(2-phenylethyl)chromone; Aquilaria
• ISSN: 1340-3443; 1861-0293
• DOI: 10.1007/s11418-020-01410-z

Agarwood has been used as an incense and in traditional medicines as aphrodisiac, sedative, cardiotonic, and carminative. In this study, five new 2-(2-phenylethyl)chromones ( 2 , 13 – 16 ) and eleven known compounds ( 1 , 3 – 12 ) were isolated from the agarwood. The structures of the new compounds were determined by 1 H-, 13 C-, and two-dimensional NMR together with electronic circular dichroism (ECD) spectroscopy. All isolated compounds were evaluated for the phosphodiesterase (PDE) 3A and 5A1 inhibitory activity by the fluorescence polarization method. Dimeric 2-(2-phenylehyl)chromones ( 13 , 14 , 16) had potent inhibitory activity to PDE 5A1 with IC 50 values of micro molar range ( 13 : 4.2 μM, 14 : 7.9 μM, 16 : 4.3 μM), whereas they had weak activity to PDE 3A. In contrast, compound ( 15 ), which has a phenylpropionic acid moiety instead of the 2-(2-phenylethyl)chromone moiety in the dimers, showed moderate inhibition of both PDE 3A (IC 50 : 42.6 μM) and PDE 5A1 (IC 50 : 15.1 μM).