Novel terpestacin derivatives with L-amino acid residue as anticancer agents against U87MG-derived glioblastoma stem cells

Based on the natural product terpestacin, seventeen derivatives (1-17) with various L-amino acid side chains were designed and synthesized. Their anticancer activities against U87MG-derived glioblastoma stem cells (GSCs) were evaluated, and compounds 5, 11, 13 and 15 showed strong abilities to inhibit the proliferation (IC50 = 2.8-6.9 mu M) and tumorsphere formation of GSCs. Besides, compounds 13 and 15 could effectively induce apoptosis and significantly inhibit the invasion of GSCs (95 and 97 % inhibition, respectively, at 2.5 mu M). The levels of CD133 marker in GSCs also decreased in dose-dependent manners after the treatment of these active compounds. Compared to terpestacin and the positive control A1938, our derivatives showed stronger activities and compounds 13 and 15 are promising candidates for further development as anticancer agents by targeting GSCs.

Automated summary

Seventeen derivatives (1-17) with different L-amino acid side chains were designed and synthesized based on the natural product terpestacin. The anticancer activities of these derivatives against U87MG-derived glioblastoma stem cells (GSCs) were evaluated, and compounds 5, 11, 13, and 15 exhibited strong inhibitory effects on GSCs' proliferation and tumorsphere formation. In addition, compounds 13 and 15 effectively induced apoptosis and significantly hindered the invasion of GSCs. The levels of CD133, a marker in GSCs, also decreased in a dose-dependent manner after treatment with these active compounds. Compared to terpestacin and the positive control A1938, our derivatives demonstrated stronger activities, with compounds 13 and 15 considered promising candidates for further development as anticancer agents targeting GSCs.