Some Novel Oxirane-Thiirane Derivatives: Synthesis, Molecular docking and Enzymatic Inhibition for Therapeutic Potential.

IF 1.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Vagif Farzaliyev, Adem Ertürk, Afat Huseynova, Yeliz Demir, Hatice Kızıltaş, Afsun Sujayev, Mir Ali İsakov, Beyim Ibrahimova, İlhami Gülçin
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引用次数: 0

Abstract

In this study, a series of new oxirane and thiirane (2a-g), were assessed for their influence on various metabolic enzymes, including acetylcholinesterase (AChE) and human carbonic anhydrase isoenzymes (hCA I and hCA II). So, in the first stage, 1-chloro-3-phenothiazylpropanol-2 (2), methyl, methoxy-substituted oxirane, thiirane (2a and 2b), methyl, 1,2-aminopropanethiols (2c-2f), trifluorinated aminethiol derivative (2g), have been synthesized. The structures of synthesized compound were confirmed by IR, NMR analysis. Enzyme inhibition studies demonstrated that all these compounds exhibited potent inhibitory effects on all the target enzymes, surpassing the standard inhibitors, as evidenced by their IC50 and Ki values. The Ki values for the compounds concerning AChE, hCA I, and hCA II enzymes were in the ranges of 1.21 ± 0.072-12.64 ± 0.12, 5.93 ± 0.028- 81.87 ± 12.52 and 61.43 ± 10.01-344.22 ± 33.87 nM, respectively. Additionally, molecular docking studies were conducted to investigate further the binding interactions of the most potent inhibitors with enzyme active sites, revealing strong hydrogen bonding, π-stacking, and halogen interactions. These findings indicate that the synthesized compounds exhibit high affinity and specificity for the target enzymes, suggesting their potential for further development as therapeutic agents. Future studies will focus on optimizing the structural features of these compounds to enhance their selectivity and bioavailability, conducting in vivo evaluations to assess their pharmacokinetic and pharmacodynamic properties, and exploring their potential applications in the treatment of neurodegenerative and metabolic disorders.

一些新的氧烷-硫烷衍生物:合成、分子对接和酶抑制的治疗潜力。
本研究评估了一系列新的氧环烷和硫代烷(2a-g)对各种代谢酶的影响,包括乙酰胆碱酯酶(AChE)和人碳酸酐酶同工酶(hCA I和hCA II),因此,在第一阶段合成了1-氯-3-吩噻嗪基丙醇-2(2)、甲基甲氧基取代氧环烷、硫代烷(2a和2b)、甲基1,2-氨基丙基硫醇(2c-2f)、三氟化氨基硫醇衍生物(2g)。合成的化合物结构经红外光谱、核磁共振分析证实。酶抑制研究表明,这些化合物对所有的靶酶都有较强的抑制作用,其IC50和Ki值证明了这些化合物对标准抑制剂的抑制作用。AChE、hCA I和hCA II酶相关化合物的Ki值分别为1.21±0.072 ~ 12.64±0.12、5.93±0.028 ~ 81.87±12.52和61.43±10.01 ~ 344.22±33.87 nM。此外,分子对接研究进一步研究了最有效的抑制剂与酶活性位点的结合相互作用,揭示了强氢键、π堆积和卤素相互作用。这些结果表明,合成的化合物对靶酶具有较高的亲和力和特异性,表明它们具有进一步开发作为治疗剂的潜力。未来的研究将集中在优化这些化合物的结构特征以提高其选择性和生物利用度,进行体内评价以评估其药代动力学和药效学特性,并探索其在治疗神经退行性和代谢性疾病方面的潜在应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cell Biochemistry and Biophysics
Cell Biochemistry and Biophysics 生物-生化与分子生物学
CiteScore
4.40
自引率
0.00%
发文量
72
审稿时长
7.5 months
期刊介绍: Cell Biochemistry and Biophysics (CBB) aims to publish papers on the nature of the biochemical and biophysical mechanisms underlying the structure, control and function of cellular systems The reports should be within the framework of modern biochemistry and chemistry, biophysics and cell physiology, physics and engineering, molecular and structural biology. The relationship between molecular structure and function under investigation is emphasized. Examples of subject areas that CBB publishes are: · biochemical and biophysical aspects of cell structure and function; · interactions of cells and their molecular/macromolecular constituents; · innovative developments in genetic and biomolecular engineering; · computer-based analysis of tissues, cells, cell networks, organelles, and molecular/macromolecular assemblies; · photometric, spectroscopic, microscopic, mechanical, and electrical methodologies/techniques in analytical cytology, cytometry and innovative instrument design For articles that focus on computational aspects, authors should be clear about which docking and molecular dynamics algorithms or software packages are being used as well as details on the system parameterization, simulations conditions etc. In addition, docking calculations (virtual screening, QSAR, etc.) should be validated either by experimental studies or one or more reliable theoretical cross-validation methods.
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