分子对接研究、希夫碱的合成及其作为 Hsp90 抑制剂的生物评价。
Molecular docking study, synthesis and biological evaluation of Schiff bases as Hsp90 inhibitors.
机构信息
Department of Pharmaceutical Chemistry, Gokaraju Rangaraju College of Pharmacy, Osmania University, Bachupally, Hyderabad, India; R&D centre, Department of Pharmaceutical Sciences, Jawaharlal Nehru Technological University, Hyderabad, India.
Department of Pharmaceutical Chemistry, Gokaraju Rangaraju College of Pharmacy, Osmania University, Bachupally, Hyderabad, India.
出版信息
Biomed Pharmacother. 2014 Apr;68(3):369-76. doi: 10.1016/j.biopha.2014.01.003. Epub 2014 Jan 15.
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, (1)HNMR 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.
热休克蛋白 90（Hsp90）是发现新型癌症治疗药物的新兴有吸引力的靶标。对接方法是生成和优化先导化合物的强大计算工具。在我们合理开发针对 Hsp90 的新型有效小分子的任务中，我们通过 Sybyl surflex Geom X 对接方法预测了我们设计的化合物的效力。上述研究的结果表明，源自 2,4-二羟基苯甲醛/5-氯-2,4-二羟基苯甲醛的席夫碱与蛋白质表现出有效的结合。随后，合成了其中的一些（1-10），并通过 IR、（1）HNMR 和质谱分析进行了表征。通过孔雀绿测定法评估合成分子抑制 Hsp90 ATP 酶活性的潜力。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）测定法进行抗癌研究。软件生成的结果与评估的生物活性非常吻合。
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