Structural Modification, Anticancer Activity Evaluation and Structure-Activity Relationship Studies Based on the Bioactive Ent-Kaurene Diterpenoid 5F From Pteris Semipinnata

For many years, plants have been considered as one of the primary sources to discovery lead compounds for drug development. Plants in the genus Pteris of the Pteridaceae family have been extensively studied due to their richly containing bioactive ent-kaurene diterpenoids, a diverse class of compounds that have been found to possess a broad spectrum of pharmacological activities, including anticancer and antibacterial activities.

Oridonin and eriocalyxin B, two representative ent-kaurenes isolated from Isodon plants, have been reported to exhibit considerable antitumor and anti-inflammatory effects¹. As another ent-kaurene diterpenoid, ent-I lα-hydroxy-15-oxokaur-l6-en- 19-oic acid (5F) is richly found in Pteris semipinnata. It has also has been demonstrated to show moderate cytotoxicity against a panel of cancer cell lines comprising HL-60, MGC-803, CNE-2Z and BEL-7402 carcinoma cells with IC50 values of 26.4, 49.6, 43.3, 74.2 µM, respectively². To improve the bioactivity and explore its antitumor drug development potential, we designed this synthetic study to prepare the analogues of 5F based on the chemical modification of the functional groups. Here, we report synthesis and bioactivity evaluation of a series of novel analogues derived from 5F.