No abstract

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.

This study developed a facile and efficient synthetic strategy to construct quaternary chiral centers at the α-position of imines and ketones. High regioselectivity and diastereoselectivity were achieved through the synergetic effect of electron-withdrawing directing groups and N-tert-butyl sulfinamide as chiral auxiliaries. Either of them could be removed under the optimized conditions without any epimerization.

No abstract

Triple-negative breast cancer (TNBC) has been considered the most aggressive and mortal breast cancer. Thus far, it remains an important challenge to develop TNBC targeted therapy. As revealed from numerous recent studies, ANXA2 may be a potential target to treat TNBC. In the present study, a natural product 5α-epoxyalantolactone (5α-EAL) was discovered as an anti-breast cancer stem cells (BCSCs) lead compound. Furthermore, 5α-EAL was found to be able to notably suppress the function of ANXA2 by covalently targeting cysteine 9 (Cys9) of ANXA2. To the best of our knowledge, 5α-EAL was recognized as the first small molecule functional inhibitor of ANXA2. It could significantly inhibit the formation of the heterotetrameric complex of ANXA2 and S100A10, which is capable of transporting E-cadherin (E-Ca) to the membrane. The above findings may be used as a possible strategy to develop novel anti-TNBC therapies targeting ANXA2.