Synthesis and Discovery Novel Anti-Cancer Stem Cells Compounds Derived from the Natural Triterpenoic Acids

Cancer
stem cells (CSCs) have been reported to be involved in tumorigenesis,
tumor recurrence, cancer invasion, metastasis, and drug-resistance.
Therefore, the development of drug molecules targeting CSCs has become
an attractive therapeutic approach. However, the molecules which can
selectively ablate CSCs are extremely rare. To explore the leading
compounds targeting CSCs, 52 analogues of triterpenoic acids were
synthesized in this study, whose biological activities were evaluated.
On the basis of the results of tumorsphere assay, two compounds 48 and 51, derived from oleanolic acid, exhibited
suppressive effect on elimination of different type of CSCs. Meanwhile,
compounds 48 and 51 could significantly
inhibit the growth of several tumors both in vitro and in vivo. Furthermore,
treatment of cancer cells with both of two compounds would dramatically
increase the level of ROS, which might eliminate the CSCs. Collectively,
the leading compounds 48 and 51 were promising
anti-CSCs agents that merited further validation as a novel class
of chemotherapeutics.