1127352-16-2Relevant academic research and scientific papers
Exploring diverse-ring analogues on combretastatin a4 (Ca-4) olefin as microtubule-targeting agents
Gao, Jin-Ming,He, Qiu-Rui,Jiang, Tian-Cheng,Song, Ming-Yu,Tang, Jiang-Jiang,Wang, Hao-Ran,Wang, Yi-Lin
, (2020/03/13)
Combretastatin-4 (CA-4) as a tubulin polymerization inhibitor draws extensive attentions. However, due to its weak stability of cis-olefin and poor metabolic stability, structure modifications on cis-configuration are being performed. In this work, we constructed a series of novel CA-4 analogues with linkers on olefin containing diphenylethanone, cis-locked dihydrofuran, α-substituted diphenylethanone, cyclobutane and cyclohexane on its cis-olefin. Cytotoxic activity of all analogues was measured by an SRB assay. Among them, compound 6b, a by-product in the preparation of diphenylethanone analogues, was found to be the most potent cytotoxic agents against HepG2 cells with IC50 values of less than 0.5 μM. The two isomers of 6b induced cellular apoptosis tested by Annexin V-FITC and propidium iodide (PI) double staining, arrested cells in the G2/M phase by PI staining analysis, and disrupted microtubule network by immunohistochemistry study in HepG2 cells. Moreover, 6b-(E) displayed a dose-dependent inhibition effect for tubulin assembly in in vitro tubulin polymerization assay. In addition, molecular docking studies showed that two isomers of 6b could bind efficiently at colchicine binding site of tubulin similar to CA-4.
A novel approach to combretastatins: From trans-epoxide to CA-4 and its dioxolane derivative
Lupattelli, Paolo,D'Auria, Maurizio,Di Blasio, Nadia,Lenti, Francesca
supporting information; experimental part, p. 141 - 145 (2009/06/28)
The trans-epoxide derivative of Combretastatin A-4 was stereoselectively prepared in good yield by sulfur ylide mediated epoxidation of silyl-protected isovanillin. From this key intermediate, a formal synthesis of CA-4, by stereoselective deoxygenation and photoisomerization, was achieved. Alternatively, a trans-dioxolane derivative was obtained by stereoselective acetone insertion. Wiley-VCH Verlag GmbH & Co. KGaA, 2009.
