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筛选新型化合物作为碳酸酐酶的潜在抑制剂及光系统II的光合活性研究

Screening of novel chemical compounds as possible inhibitors of carbonic anhydrase and photosynthetic activity of photosystem II.

作者信息

Karacan Mehmet Sayım, Zharmukhamedov Sergei K, Mamaş Serhat, Kupriyanova Elena V, Shitov Alexandr V, Klimov Vyacheslav V, Özbek Neslihan, Özmen Ümmühan, Gündüzalp Ayla, Schmitt Franz-Josef, Karacan Nurcan, Friedrich Thomas, Los Dmitry A, Carpentier Robert, Allakhverdiev Suleyman I

机构信息

Gazi University, Science Faculty, Department of Chemistry, 06500 Ankara, Turkey.

Institute of Basic Biological Problems, Russian Academy of Sciences, Institutskaya Street 2, Pushchino, Moscow Region 142290, Russia.

出版信息

J Photochem Photobiol B. 2014 Aug;137:156-67. doi: 10.1016/j.jphotobiol.2013.12.002. Epub 2013 Dec 25.

Abstract

Thirty novel chemical compounds were designed and synthesized expecting that they would be possible inhibitors. From this number eleven were organic bases, twenty-four were their organic derivatives and fourteen were metal complexes. Screening of these chemicals by their action on photosynthetic electron transfer (PET) and carbonic anhydrase (CA) activity (CAA) of photosystem II (PSII), α-CA, as well as β-CA was done. Several groups were revealed among them. Some of them are capable to suppress either one, two, three, or even all of the measured activities. As example, one of the Cu(II)-phenyl sulfonylhydrazone complexes (compound 25) suppresses CAA of α-CA by 88%, CAA of β-CA by 100% inhibition; CAA of PSII by 100% and the PSII photosynthetic activity by 66.2%. The Schiff base compounds (12, 15) and Cu(II)-phenyl sulfonylhydrazone complexes (25, 26) inhibited the CAA and PET of PSII significantly. The obtained data indicate that the PSII donor side is a target of the inhibitory action of these agents. Some physico- or electrochemical properties such as diffusion coefficient, number of transferred electrons, peak potential and heterogeneous standard rate constants of the compounds were determined in nonaqueous media. pKa values were also determined in nonaqueous and aqueous media. Availability in the studied group of novel chemical agents possessing different inhibitory activity allow in future to isolate the "active part" in the structure of the inhibitors responsible for different inhibitory mechanisms, as well as to determine the influence of side substituters on its inhibitory efficiency.

摘要

设计并合成了30种新型化合物,期望它们可能成为抑制剂。其中11种是有机碱,24种是它们的有机衍生物,14种是金属配合物。通过这些化合物对光合系统II(PSII)的光合电子传递(PET)和碳酸酐酶(CA)活性(CAA)、α - CA以及β - CA的作用进行了筛选。结果发现它们可分为几组。其中一些能够抑制所测活性中的一种、两种、三种甚至全部。例如,一种Cu(II)-苯磺酰腙配合物(化合物25)对α - CA的CAA抑制率为88%,对β - CA的CAA抑制率为100%;对PSII的CAA抑制率为100%,对PSII光合活性抑制率为66.2%。席夫碱化合物(12、15)和Cu(II)-苯磺酰腙配合物(25、26)显著抑制了PSII的CAA和PET。所得数据表明PSII供体侧是这些药剂抑制作用的靶点。在非水介质中测定了这些化合物的一些物理或电化学性质,如扩散系数、转移电子数、峰电位和异质标准速率常数。还在非水和水介质中测定了pKa值。所研究的具有不同抑制活性的新型化学药剂组的存在,使得未来能够分离出抑制剂结构中负责不同抑制机制的“活性部分”,并确定侧链取代基对其抑制效率的影响。

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