Abstract
A series of 3-(3′-hydroxy-4′-methoxyphenyl)selenyl-5,6,7-trimethoxy-1H-indoles and 3-(3′-hydroxy-4′-methoxyphenyl)thio-5,6,7-trimethoxy-1H-indoles were obtained as a new class of combretastatin A-4 (CA-4) analogues via a convenient ultrasound (US)-assisted two-step process involving 3-selenenylation/sulfenylation followed by O-deallylation. With the assistance of US irradiation, both the reaction rates and yields of selenenylation, sulfenylation and O-deallylation could be significantly improved. A comparison of the reaction rates of O-deallylation and ester reduction demonstrated that O-deallylation was more sensitive to US irradiation. Finally, these products were evaluated for their antiproliferative activities, and most of them showed moderate to potent activities against three human cancer cell lines in vitro.
Highlights
A series of 3-(3′-hydroxy-4′-methoxyphenyl)selenyl-5,6,7-trimethoxy-1H-indoles and 3-(3′-hydroxy4′-methoxyphenyl)thio-5,6,7-trimethoxy-1H-indoles were obtained as a new class of combretastatin A-4 (CA-4) analogues via a convenient ultrasound (US)-assisted two-step process involving 3-selenenylation/sulfenylation followed by O-deallylation
CombretastatinA-4 (CA-4, 1a, Fig. 1), a natural stilbene isolated from the South African tree Combretum caffrum, is a powerful inhibitor of tubulin polymerization that displays cytotoxic and antivascular activities by binding at the colchicine site of tubulin[1]
The structure-activity relationship (SAR) study of CA-4 indicated that the presence of a cis-double bond and 3,4,5-trimethoxyphenyl ring-A is essential for its anti-tubulin activity, and the introduction of a hydroxyl group to the C′ -3 position in ring-B was found to strongly enhance its activity
Summary
Zhiyong, Xiaona Li, Daiying Zuo, Binyue Lang, Yang Wu, Mingyang Jiang, Huizhuo Ma, Kai Bao, Yingliang Wu, and Weige Zhang. 2016. We reported the development of a set of 3-arylselenylindoles (5) as CA-4 analogues, which exhibited potent activities in the tubulin polymerization inhibition and against three human cancer cell lines[12]. The effects of the most potent compound, 10a, on the inhibition of tubulin assembly were tested in vitro by immunofluorescence studies
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