Design, Synthesis and in vitro Cytotoxicity Evaluation of New 3′,4′-bis(3,4,5-trisubstituted)-4′H-spiro[indene-2,5′-isoxazol]-1(3H)-one Derivatives as Promising Anticancer Agents

被引：9

作者：

Abolhasani, Hoda ^{[1
,2
,3
]}

Zarghi, Afshin ^{[4
]}

Abolhasani, Ahmad ^{[5
]}

Hamzeh-Mivehroud, Maryam ^{[1
,3
]}

Bargahi, Nasrin ^{[1
,6
]}

Notash, Behrouz ^{[7
]}

Mojarradand, Javid Shahbazi ^{[3
]}

Dastmalchi, Siavoush ^{[1
,3
]}

机构：

[1] Tabriz Univ Med Sci, Biotechnol Res Ctr, Tabriz, Iran

[2] Tabriz Univ Med Sci, Student Res Comm, Tabriz, Iran

[3] Tabriz Univ Med Sci, Sch Pharm, Dept Med Chem, Tabriz, Iran

[4] Shahid Beheshti Univ Med Sci, Sch Pharm, Dept Med Chem, Tehran, Iran

[5] Isfahan Univ, Fac Adv Sci & Technol, Dept Biotechnol, Esfahan, Iran

[6] Tabriz Univ Med Sci, Drug Appl Res Ctr, Tabriz, Iran

[7] Shahid Beheshti Univ, Dept Chem, GC, Tehran 1983963113, Iran

来源：

LETTERS IN DRUG DESIGN & DISCOVERY | 2014年 / 11卷 / 10期

关键词：

Antitubulin; COX-2; inhibitor; 1,3-dipolar cycloaddition; hybrid compounds; MTT assay; spiro-isoxazoline; 1,3-DIPOLAR CYCLOADDITION REACTIONS; ANTIMITOTIC NATURAL-PRODUCTS; ONE-POT SYNTHESIS; SPIRO-ISOXAZOLINE; ANTINEOPLASTIC AGENTS; BIOLOGICAL EVALUATION; TUBULIN INHIBITOR; COMBRETASTATIN A4; CANCER; COLCHICINE;

D O I：

10.2174/1570180811666140704172442

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new series of 3',4'-bis(3,4,5-trimethoxyphenyl)-4'H-spiro[indene-2,5'-isoxazol]-1(3H)-one derivatives was designed and synthesized. The cytotoxic effects of the synthesized compounds were evaluated on several different human cancer cells. Among them, compound 9e displayed the most potent in vitro antiproliferative activity with IC50 values of 0.07 +/- 0.01 mu M on T47D cells. Another potent derivative 9h displayed an IC50 value of 0.12 +/- 0.07 mu M against T47D cells, comparable to that of the positive controls (Colchicine Cisplatin Vincristine Vinblastine Doxorubicin Celecoxib). The structure-activity relationships were discussed and both anti-tubulin and COX-2 inhibitory effects were proposed for the developed compounds.

引用

页码：1149 / 1161

页数：13

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