1 research outputs found
Total Syntheses and Biological Activities of Vinylamycin Analogues
Natural
depsipeptide vinylamycin was reported to be an antibiotic
previously. Herein we report vinylamycin to be active against K562
leukemia cells (IC<sub>50</sub> = 4.86 μM) and be unstable in
plasma (<i>t</i><sub>1/2</sub> = 0.54 h). A total of 24
vinylamycin analogues with modification of the OH group and chiral
centers were generated via a combinatorial approach. The lead compound <b>1a</b> was subsequently characterized as having the following:
no antimicrobial activity, significantly higher plasma stability (<i>t</i><sub>1/2</sub> = 14.3 h), improved activity against K562
leukemia cells (IC<sub>50</sub> = 0.64 μM), and up to 75% cell
inhibition without significant toxicities in K562 cells xenograft
zebrafish model. Furthermore, compound <b>1a</b> maintained
its activity against the breast cancer cell line MCF-7 under hypoxic
conditions. In comparison, the activity of gemcitabine in the same
hypoxic in vitro model of MCF-7 cells was 15-fold lower. Therefore,
the present results demonstrate that <b>1a</b> has great potential
as an anticancer agent