9-amino-5-alkyl-12(H)-quino[3,4-b][1,4]benzothiazine chloride 与主要载体血浆蛋白的体外光谱研究。

IF 4.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemico-Biological Interactions Pub Date : 2024-10-23 DOI:10.1016/j.cbi.2024.111289

Aleksandra Owczarzy , Monika Trzepacz , Karolina Kulig , Wojciech Rogóż , Andrzej Zięba , Małgorzata Maciążek-Jurczyk

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引用次数: 0

摘要

目前的癌症治疗方法，尤其是化疗，都会产生有害的副作用。因此，研究具有抗癌潜力的新物质，尽可能提高疗效，减少副作用，意义重大。本研究的目的是对 9-氨基-5-烷基-12(H)-喹啉并[3,4-b][1,4]苯并噻嗪氯化物（Salt3）与主要载体蛋白（如人血清白蛋白（HSA）、α1 酸糖蛋白（AGP）、人γ球蛋白（HGG）和对照正常血清（CNS））之间的相互作用进行光谱分析。利用 Klotz 方程计算了 Salt3 与所研究的载体蛋白和对照正常血清结合的结合常数（Ka [mol-L-1]）和结合位点类别数（n）。为了研究 HSA 和 AGP 的高亲和性结合位点，使用了荧光标记物。光谱参数 A 和差分吸收光谱的二次导数用于评估芳香族氨基酸残基周围的环境变化。利用圆二色性分析评估了与 Salt3 复合物中 HSA 和 AGP 二级结构的变化。Salt3 与 HSA、AGP、HGG 分子和 CNS 有轻微结合。此外，Salt3 还会影响所研究蛋白质的三级结构，而不会破坏负责 Salt3 在血液中分布的主要载体蛋白质的二级结构。由于 Salt3 与模型载体蛋白和正常对照血清的结合力很弱，因此它既能产生强烈的治疗作用，也能产生毒性作用。考虑到这些初步的光谱研究，似乎有必要进行更多的测试，并将研究扩展到其他技术。

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In vitro spectroscopic studies of 9-amino-5-alkyl-12(H)-quino[3,4-b][1,4]benzothiazine chloride with main carrier plasma proteins

Current methods of cancer treatment, particularly chemotherapy, are associated with harmful side effects. For this reason, it is significant to study new substances with anticancer potential with the highest possible efficacy and the lowest possible side effects. The aim of the study was the spectroscopic analysis of the interaction between 9-amino-5-alkyl-12(H)-quino[3,4-b][1,4]benzothiazine chloride (Salt3) and main carrier proteins, such as human serum albumin (HSA), α1 acid glycoprotein (AGP), human γ globulin (HGG) and controlled normal serum (CNS).

The association constants (K_a [mol·L⁻¹]) and the number of binding site classes (n) for the binding of Salt3 with studied carrier proteins and controlled normal serum were calculated using the Klotz equation. To study HSA and AGP high affinity binding sites, the fluorescent markers were used. Spectral parameter A and the second derivative of differential absorption spectra were used to assess environmental changes around aromatic amino acids residues. The changes in HSA and AGP secondary structure in the complexes with Salt3 were evaluated using the analysis using circular dichroism.

Salt3 slightly binds to HSA, AGP, HGG molecules and CNS. In addition, Salt3 affects the tertiary structure of the studied proteins, while it does not damage the secondary structure of the main carrier proteins responsible for Salt3 distribution in the bloodstream.

Because Salt3 binds weakly to model carrier proteins and normal control serum, it can lead to both strong therapeutic and toxic effects. Considering these preliminary spectroscopic studies, additional tests as well as expanding research to include other techniques seem justified.

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来源期刊

Chemico-Biological Interactions 生物-毒理学

CiteScore

7.70

自引率

3.90%

发文量

410

审稿时长

36 days

期刊介绍： Chemico-Biological Interactions publishes research reports and review articles that examine the molecular, cellular, and/or biochemical basis of toxicologically relevant outcomes. Special emphasis is placed on toxicological mechanisms associated with interactions between chemicals and biological systems. Outcomes may include all traditional endpoints caused by synthetic or naturally occurring chemicals, both in vivo and in vitro. Endpoints of interest include, but are not limited to carcinogenesis, mutagenesis, respiratory toxicology, neurotoxicology, reproductive and developmental toxicology, and immunotoxicology.