Synthesis of steroid analogs of tubuloclustin, their cytotoxicity and effect on microtubules of A549 carcinoma cells

被引：4

作者：

Nurieva, E. V. ^{[1
]}

Zefirov, N. A. ^{[1
,2
]}

Mamaeva, A. V. ^{[1
]}

Wobith, B. ^{[3
]}

Kuznetsov, S. A. ^{[3
]}

Zefirova, O. N. ^{[1
,2
]}

机构：

[1] Moscow MV Lomonosov State Univ, Dept Chem, 1 Leninskie Gory, Moscow 119991, Russia

[2] Russian Acad Sci, Inst Physiol Act Cpds, 1 Severnyi Proezd, Chernogolovka 142432, Moscow Region, Russia

[3] Univ Rostock, Inst Biol Sci, D-18106 Rostock, Germany

来源：

RUSSIAN CHEMICAL BULLETIN | 2018年 / 67卷 / 04期

基金：

俄罗斯基础研究基金会;

关键词：

2-methoxyestradiol; adamantane; colchicine; tubuloclustin; tubulin; microtubule network; cytotoxicity; A549 lung carcinoma cells; ANTIPROLIFERATIVE ACTIVITY; 2-METHOXYESTRADIOL; ACIDS; DRUG;

D O I：

10.1007/s11172-018-2123-6

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Synthesis of analogs of tubuloclustin (N-(7-adamant-2-yloxy-7-oxoheptanoyl)-N-deacetylcolchicine (1)) with the colchicine fragment replaced with 2-methoxyestradiol scaffold attached via phenolic hydroxy group was described. Esters 3a-c exhibit moderate cytotoxicity (EC50 = 5-6 mu mol L-1) and exert a weak effect on the microtubule network in A549 human lung carcinoma cells similar to the clustering effect of tubuloclustin and its derivatives. Conjugates 6a-c and 7a-c with the phenolic ester bond are low stable and compounds 7a-c are inactive to the microtubules of A549 cells, while compounds 6a-c cause an unusual effect of curling of the microtubules.

引用

页码：688 / 693

页数：6

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