Synthesis and Evaluation of A Water-Soluble Epothilone B Prodrug with Remarkably Decreased Toxicity

Wang, Haibo; Kuang, Hongfu; Zhang, Wei; Zhou, Xiaomeng; Zhu, Tong

doi:10.2174/1570178614666161107142106

Cited by 2 publications

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Glutathione‐epothilone B ( 26 , IC 50 : 1.3 nM, MTT assay), the epothilone B prodrug, showed at least 4000 times higher solubility in water than epothilone B (21.1 vs. 0.005 mg/ml), which was more potent than epothilone B (IC 50 : 4.3 nM) against HepG2 cells. [ 70 ] The SAR proved that replacement of the 12,13‐epoxide with an aziridine moiety was favorable to the activity, and a significant part of the epothilone B analogues (IC 50 : 0.01–353.1 nM, MTT assay) was highly potent against SKBR3, SKOV3, HeLa, MDR MES SA DXE, and MES SA DX cancer cell lines, with IC 50 values in a nanomolar range. [ 71 ] In particular, the most active analogue 27 (IC 50 : 0.01–0.03 nM) was 94.3‐ to 9280‐fold more potent than epothilone B (IC 50 : 1.27–3.63 nM) and ixabepilone (IC 50 : 7.72 and 278.4 nM), so this compound warrants further investigations.…”

Section: ‐Membered Macrolactonesmentioning

confidence: 99%

Anticancer activities, structure–activity relationship, and mechanism of action of 12‐, 14‐, and 16‐membered macrolactones

Wang

2021

Archiv der Pharmazie

View full text Add to dashboard Cite

Cancer remains one of the major causes of death worldwide despite the encouraging breakthroughs in the discovery of novel chemotherapeutic agents in recent years. The development of new effective anticancer candidates still represents a challenging endeavor due to the severe anticancer demands and the emergence of drug‐resistant, especially multidrug‐resistant, cancers. Macrolactones could regulate multiple signaling pathways in cancer cells and demonstrated potential anticancer effects, including inhibition of proliferation, metastasis, and angiogenic activity. Accordingly, macrolactones possess excellent efficacy against both drug‐sensitive and drug‐resistant cancer cells, and the rational design of macrolactones may provide valuable therapeutic interventions for cancers. The purpose of this review is as follows: (1) outline the recent advances made in the development of 12‐, 14‐, and 16‐membered macrolactones with anticancer potential; (2) summarize the structure–activity relationship; and (3) discuss their anticancer mechanisms.

show abstract

Section: ‐Membered Macrolactonesmentioning

confidence: 99%