Antiproliferative Activities of Cynaropicrin and Related Compounds against Cancer Stem Cells

In this study, we evaluated the antiproliferative activities of 21 sesquiterpenoids against human GBM U-251 MG CSCs and U-251 MG non-CSCs. Particularly, the guaianolide sesquiterpene lactone cynaropicrin (1) showed strong antiproliferative activity against U-251 MG CSCs (IC50 = 20.4 µM) and U-251 MG non-CSCs (IC50 = 10.9 µM). Accordingly, we synthesized six derivatives of 1 and investigated their structure-activity relationships. Most of the guaianolide sesquiterpene lactones with the α-methylene-γ-butyrolactone moiety showed antiproliferative activities against U-251 MG cells. We conclude that the 5,7,5-ring and the α-methylene-γ-butyrolactone moiety are both important for antiproliferative activities against U-251 MG cells. The results of this study suggest that the α,β-unsaturated carbonyl moiety, which has recently become a research hotspot in drug discovery, is the active center of 1. Therefore, we consider 1 as a potential lead for developing novel drugs targeting CSCs.PMID:38382968 | DOI:10.1248/cpb.c23-00811

Source: Chemical and Pharmaceutical Bulletin - February 21, 2024 Category: Drugs & Pharmacology Authors: Kousuke Araki Minami Hara Shohei Hamada Takahiro Matsumoto Seikou Nakamura Source Type: research