jm8b01141_si_002.csv (5.15 kB)
Improved Total Synthesis and Biological Evaluation of Coibamide A Analogues
dataset
posted on 2018-09-21, 20:45 authored by Guiyang Yao, Wei Wang, Lijiao Ao, Zhehong Cheng, Chunlei Wu, Zhengyin Pan, Ke Liu, Hongchang Li, Wu Su, Lijing FangTo
enable the large-scale synthesis of coibamide A, we developed
an improved synthetic strategy for this class of cyclodepsipeptide.
The versatility of the synthetic procedure was demonstrated by the
preparation of a series of designed coibamide A analogues, which enabled
the preliminary structure–activity relationship (SAR) studies
for this compound. Although most modifications of coibamide A resulted
in decrease or loss of the antiproliferativity, we found that versatile
substitution at position 3 was well tolerated. Remarkably, a simplified
analogue, [MeAla3-MeAla6]-coibamide (1f), not only showed
nearly the same inhibition as coibamide A against the tested cancer
cells but also significantly inhibited tumor growth in vivo. The improved
synthetic strategy and the relevant trends of SAR disclosed in this
study will be valuable for further optimization of the overall profile
of coibamide A.