1620886-01-2Relevant academic research and scientific papers
Ferrocenyl 2,5-Piperazinediones as Tubulin-Binding Organometallic ABCB1 and ABCG2 Inhibitors Active against MDR Cells
Wieczorek, Anna,B?auz, Andrzej,Zakrzewski, Janusz,Rychlik, B?azej,Plazuk, Damian
, p. 612 - 617 (2016)
The tubulin-microtubule system is a common target of many anticancer drugs. However, the use of chemotherapeutics frequently leads to the development of a clinically relevant phenomenon of multidrug resistance (MDR). One of the basic mechanisms involved in MDR involves elevated expression and/or activity of several ATP-binding cassette superfamily members (ABC transporters) which are normally responsible for the efflux of xenobiotics or secondary metabolites outside the cell. Here we present the synthesis and biological characteristics of ferrocenyl analogues of plinabulin, i.e. one of the so-called "spindle poisons". We found that replacement of the phenyl group of plinabulin by the ferrocenyl moiety turns this compound into a potent inhibitor of ABCB1 and ABCG2, thus making it possible to overcome the multidrug resistance phenomenon. We also demonstrated that the alkyl group attached to the imidazole moiety of ferrocenyl analogues of plinabulin strongly affects their potency to inhibit tubulin polymerization.
Tubulin inhibitor
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Paragraph 0058; 0059; 0060, (2017/08/28)
The invention provides a novel tubulin inhibitor and an application thereof. The novel tubulin inhibitor is a series of substituted heterocyclic skeleton-based compounds with colchicine binding sites in tubulins as targets. The compounds have the following structure as shown in the specification, wherein the formula is as shown in the specification; n independently represents an integer of 0-5 under the condition that n is less than or equal to 5; A represents a monosubstituted or polysubstituted group; and the group is selected from H, C1-C20 acylamino, C1-C20 acyloxy, C1-C20 alkanoyl, C1-C20 alkoxycarbonyl, C1-C20 alkoxy, C1-C20 alkylamino, C1-C20 alkylcarboxy amino, aroyl, arylalkanoyl, carboxyl, cyano, halogen, hydroxyl, nitro and methylthienyl.
Design and synthesis of novel soluble 2,5-diketopiperazine derivatives as potential anticancer agents
Liao, Shengrong,Qin, Xiaochu,Li, Ding,Tu, Zhengchao,Li, Jinsheng,Zhou, Xuefeng,Wang, Junfeng,Yang, Bin,Lin, Xiuping,Liu, Juan,Yang, Xianwen,Liu, Yonghong
, p. 236 - 244 (2014/07/08)
Non-protected 2,5-diketopiperazine derivatives have poor solubility thus with negative impact on their bioavailability. In the present study, twenty-one novel soluble mono-protected, and three non-protected 2,5-diketopiperazine derivatives were designed and synthesized. Their anticancer activity to ten cell lines were evaluated by using CCK8 assay, and the results showed that about half of the mono-protected derivatives had broad-spectrum anticancer activity. Among allyl-protected derivatives, compound 4m had strong activity to all the cell lines (IC50 = 0.5-4.5 μM), especially to the cancer cell lines U937 (IC50 = 0.5 μM) and K562 (IC50 = 0.9 μM). Compound 4m could become a lead compound for further development for anticancer agents.
