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一项针对polo样激酶-1酶的酶信息学研究:对从熊耳草叶片中分离出的化合物的抗癌潜力的比较评估。

An enzoinformatics study targeting polo-like kinases-1 enzyme: Comparative assessment of anticancer potential of compounds isolated from leaves of Ageratum houstonianum.

作者信息

Rizvi Syed Mohd Danish, Shakil Shazi, Zeeshan Mohd, Khan Mohd Sajid, Shaikh Sibhghatulla, Biswas Deboshree, Ahmad Adnan, Kamal Mohammad Amjad

机构信息

Department of Biosciences, Integral University, Lucknow, Uttar Pradesh, India.

Department of Bioengineering, Integral University, Lucknow, Uttar Pradesh, India.

出版信息

Pharmacogn Mag. 2014 Jan;10(Suppl 1):S14-21. doi: 10.4103/0973-1296.127333.

Abstract

Natural products from plant sources, embracing inherently ample structural diversity than synthetic ones are the major sources of anticancer agents and will constantly play as protagonists for discovering new drugs. Polo-like kinases (PLKs) play a leading role in the ordered execution of mitotic events and 4 mammalian PLK family members have been identified. PLK1 is an attractive target for anticancer drugs in mammalian cells, among the four members of PLKs. The present study expresses the molecular interaction of compounds (1,2-Benzenedicarboxylic acid bis (2 ethylhexyl) ester, squalene, 3,5-bis (1,1-dimethylethyl) phenol, Pentamethyl tetrahydro-5H-chromene, (1,4-Cyclohexylphenyl) ethanone and 6-Vinyl-7-methoxy-2,2-dimethylchromene) isolated from methanolic extract of leaves of Ageratum houstonianum with PLK1 enzyme. Docking between PLK1 and each of these compounds (separately) was performed using "Auto dock 4.2." (1,4-Cyclohexylphenyl) ethanone showed the maximum potential as a promising inhibitor of PLK1 enzyme with reference to ∆G (-6.84 kcal/mol) and Ki (9.77 μM) values. This was sequentially followed by Pentamethyl tetrahydro-5H-chromene (∆G = -6.60 kcal/mol; Ki = 14.58 μM), squalene (∆G = -6.17 kcal/mol; Ki = 30.12 μM), 6-Vinyl-7-methoxy-2,2-dimethylchromene (∆G = -5.91 kcal/mol; Ki = 46.68 μM), 3, 5-bis (1,1-dimethylethyl) phenol (∆G = -5.70 kcal/mol; Ki = 66.68 μM) and 1,2-Benzenedicarboxylic acid bis (2 ethylhexyl) ester (∆G = -5.58 kcal/mol; Ki = 80.80 μM). These results suggest that (1,4-Cyclohexylphenyl) ethanone might be a potent PLK1 inhibitor. Further, in vitro and in vivo rumination are warranted to validate the anticancer potential of (1,4-Cyclohexylphenyl) ethanone.

摘要

植物源天然产物比合成产物具有更丰富的内在结构多样性,是抗癌药物的主要来源,并将持续在新药发现中发挥主角作用。Polo样激酶(PLKs)在有丝分裂事件的有序执行中起主导作用,已鉴定出4种哺乳动物PLK家族成员。在PLKs的4个成员中,PLK1是哺乳动物细胞中抗癌药物的一个有吸引力的靶点。本研究表达了从藿香蓟叶片甲醇提取物中分离出的化合物(邻苯二甲酸二(2-乙基己基)酯、角鲨烯、3,5-双(1,1-二甲基乙基)苯酚、五甲基四氢-5H-色烯、(1,4-环己基苯基)乙酮和6-乙烯基-7-甲氧基-2,2-二甲基色烯)与PLK1酶的分子相互作用。使用“自动对接4.2”对PLK1与这些化合物(分别)进行对接。参照∆G(-⁶.⁸⁴千卡/摩尔)和Ki(⁹.⁷⁷微摩尔)值,(1,4-环己基苯基)乙酮作为PLK1酶的一种有前景的抑制剂显示出最大潜力。其次依次是五甲基四氢-5H-色烯(∆G = -⁶.⁶⁰千卡/摩尔;Ki = ¹⁴.⁵⁸微摩尔)、角鲨烯(∆G = -⁶.¹⁷千卡/摩尔;Ki = ³⁰.¹²微摩尔)、6-乙烯基-7-甲氧基-2,2-二甲基色烯(∆G = -⁵.⁹¹千卡/摩尔;Ki = ⁴⁶.⁶⁸微摩尔)、3,5-双(1,1-二甲基乙基)苯酚(∆G = -⁵.⁷⁰千卡/摩尔;Ki = ⁶⁶.⁶⁸微摩尔)和邻苯二甲酸二(2-乙基己基)酯(∆G = -⁵.⁵⁸千卡/摩尔;Ki = ⁸⁰.⁸⁰微摩尔)。这些结果表明(1,4-环己基苯基)乙酮可能是一种有效的PLK1抑制剂。此外,需要进行体外和体内研究以验证(1,4-环己基苯基)乙酮的抗癌潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b3c/4047579/07e91dd6ed9c/PM-10-14-g001.jpg

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