Protein Tyrosine Phosphatase 1B Inhibitory Iridoids from Psydrax subcordata

• Published in: Journal of natural products (Washington, D.C.) Vol. 82; no. 10; pp. 2916 - 2924
• Main Authors: Zhou, Junfei, Wu, Zhenlong, Oyawaluja, Bamisaye O, Coker, Herbert A. B, Odukoya, Olukemi A, Yao, Guangmin, Che, Chun-Tao
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society and American Society of Pharmacognosy 25.10.2019; Amer Chemical Soc
• Subjects: Chemistry, Medicinal; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Plant Sciences; Science & Technology; FRUITS; IN-VITRO; PTP1B; BIOSYNTHESIS; CHARMM; DIMERS; MEDICINAL-PLANTS; DISCOVERY; CONSTITUENTS
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.9b00770

Phytochemical investigation of the leaves and bark of Psydrax subcordata has led to the isolation of six new iridoids, subcordatanols I–V (1–4 and 6) and 1-O-methylcrescentin I (5), along with two known analogues (7 and 8). Among them, subcordatanol I (1) is the first example of a 3,8-monoepoxy-iridoid featuring a caged 2-oxa-bicyclo[3.2.1]­octane core. The absolute stereochemistry at C-4 of 3, 4, and 6 was established through their acid-catalyzed reaction products subcordatalactones A (3a), B (4a), and C (6a), respectively. Subcordatanols I (1) and II (2), as well as subcordatalactones A (3a) and B (4a), displayed inhibitory activity against protein tyrosine phosphatase 1B (PTP1B). Enzyme kinetic studies indicated that 3a and 4a are competitive inhibitors. A molecular docking study is also reported.