European Journal of Medicinal Chemistry p. 15 - 31 (2019)
Update date:2022-08-15
Topics:
Shen, Qing-Kun
Deng, Hao
Wang, Shi-Ben
Tian, Yu-Shun
Quan, Zhen-Shan
A series of novel oridonin derivatives bearing various substituents on the 14-OH position were designed and synthesised. Their antitumour activity was evaluated in vitro against three human cancer cell lines (HCT116, BEL7402, and MCF7). Most tested derivatives showed improved anti-proliferative activity compared to the lead compound oridonin and the positive control drug 5-fluorouracil (5-Fu). Among them, compound C7 (IC50 = 0.16 μM) exhibited the most potent anti-proliferative activity against HCT116 cells; it was about 43- and 155-fold more efficacious than that of oridonin (IC50 = 6.84 μM) and 5-Fu (IC50 = 24.80 μM) in HCT116 cancer cells. Interestingly, the IC50 value of compound C7 in L02 normal cells was 23.6-fold higher than that in HCT116 cells; it exhibited better selective anti-proliferative activity and specificity than oridonin and 5-Fu. Furthermore, compound C7 possibly induced cell cycle arrest and apoptosis by regulating the p53-MDM2 signalling pathway. Notably, C7 displayed more significant suppression of tumour growth than oridonin in colon tumour xenograft models where the tumour growth inhibition rate was 85.82%. Therefore, compound C7 could be a potential lead compound for the development of a novel antitumour agent.
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Doi:10.1021/ma101424x
(2010)Doi:10.1016/S0040-4039(00)99432-2
(1989)Doi:10.1021/om100743z
(2010)Doi:10.1080/10426500903348013
(2010)Doi:10.1002/cmdc.201900618
(2020)Doi:10.1016/j.tetlet.2010.07.014
(2010)