Molecular docking study, synthesis and biological evaluation of Schiff bases as Hsp90 inhibitors

被引：24

作者：

Gupta, Sayan Dutta ^{[1
,3
]}

Snigdha, D. ^{[1
]}

Mazaira, Gisela I. ^{[4
]}

Galigniana, Mario D. ^{[4
,5
]}

Subrahmanyam, C. V. S. ^{[1
]}

Gowrishankar, N. L. ^{[2
]}

Raghavendra, N. M. ^{[1
]}

机构：

[1] Osmania Univ, Dept Pharmaceut Chem, Gokaraju Rangaraju Coll Pharm, Hyderabad 500007, Andhra Pradesh, India

[2] Swami Vivekananda Inst Pharmaceut Sci, Nalgonda, Andhra Pradesh, India

[3] Jawaharlal Nehru Technol Univ, Dept Pharmaceut Sci, R&D Ctr, Hyderabad, Andhra Pradesh, India

[4] Univ Buenos Aires, Fac Nat Sci, Dept Biol Chem, Buenos Aires, DF, Argentina

[5] Consejo Nacl Invest Cient & Tecn, Inst Expt Biol & Med, RA-1033 Buenos Aires, DF, Argentina

来源：

BIOMEDICINE & PHARMACOTHERAPY | 2014年 / 68卷 / 03期

关键词：

Hsp90; Schiff bases; Docking; Malachite green; MTT; SHOCK-PROTEIN; 90; SCORING FUNCTIONS; CHAPERONE HSP90; CELL-GROWTH; ASSAY; CANCER; OPTIMIZATION; COMPLEXES; BINDING;

D O I：

10.1016/j.biopha.2014.01.003

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Heat shock protein 90 (Hsp90) is an emerging attractive target for the discovery of novel cancer therapeutic agents. Docking methods are powerful in silico tools for lead generation and optimization. In our mission to rationally develop novel effective small molecules against Hsp90, we predicted the potency of our designed compounds by Sybyl surflex Geom X docking method. The results of the above studies revealed that Schiff bases derived from 2,4-dihydroxy benzaldehyde/5-chloro-2,4-dihydroxy benzaldehyde demonstrated effective binding with the protein. Subsequently, a few of them were synthesized (1-10) and characterized by IR, (HNMR)-H-1 and mass spectral analysis. The synthesized molecules were evaluated for their potential to suppress Hsp90 ATPase activity by Malachite green assay. The anticancer studies were performed by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay method. The software generated results was in satisfactory agreement with the evaluated biological activity. (C) 2014 Elsevier Masson SAS. All rights reserved.

引用

页码：369 / 376

页数：8

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