Synthesis, biological evaluation and cellular localization study of fluorescent derivatives of Jiyuan Oridonin A.

Jiyuan Oridonin A (JOA) is a naturally occurring ent -kaurane diterpenoid that exhibits significant potential in the field of anti-tumor drug development. However, its detailed anti-cancer mechanism of action has not been fully understood. In order to investigate its anticancer mode of action, two series of novel fluorescent derivatives of JOA conjugated with naphthalimide dyes were synthesized, and their antitumor activity against five selected cancer cell lines (MGC-803, SW1990, PC-3, TE-1 and HGC-27) was evaluated. Compared with JOA , the anti-tumor activity of the vast majority of compounds were improved. Among them, B12 exhibited promising anti-proliferative activity against HGC-27 cells with IC 50 value of 0.39 ± 0.09 μM. Fluorescence imaging studies demonstrated that probe B12 could enter HGC-27 cells in a dose-dependent and time-dependent manner and was mainly accumulated in mitochondria. Preliminary biological mechanism studies indicated that B12 was able to inhibit cell cloning and migration. Further studies suggested that B12 -induced apoptosis was related to the mitochondrial pathway. Overall, our results provide new approaches to explore the molecular mechanism of the natural product JOA , which would contribute to its further development as an antitumor agent. [Display omitted] • Two series of novel fluorescent derivatives of JOA were designed and evaluated for toxicity. • Compound B12 displayed the strongest inhibitory activity (IC 50 = 0.39 ± 0.09 μM) and selectivity against HGC-27 cells. • B12 could enter HGC-27 cells in a dose-dependent and time-dependent manner and was mainly accumulated in mitochondria. • Primary mechanism study indicated that B12 -induced apoptosis was related to the mitochondrial pathway. [ABSTRACT FROM AUTHOR]