基于结构的磺酰胺衍生物分析:从固态到乙酰乳酸合成酶的酶相互作用

IF 2.1 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES
Antônio S. N. Aguiar, Rogério F. Costa, Leonardo L. Borges, Lucas D. Dias, Hamilton B. Napolitano
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引用次数: 0

摘要

发现具有除草活性的无毒化合物仍然是农业杂草管理实践中的一项重大挑战。在本研究中,我们对磺胺衍生物,即磺胺嘧啶、磺胺甲基嘧啶和磺胺甲噁嗪进行了比较分析,这些衍生物通常用作抗生素药物。我们的目的是了解 -CH3 取代基对嘧啶环的影响及其作为候选除草剂的潜力。我们在气相中使用密度泛函理论的 M06-2X 混合交换相关函数和 6-311++G(d, p) 基集研究了嘧啶环的几何结构和电子结构。然后将这些几何参数与晶体学数据进行比较验证。利用前沿分子轨道能预测化学反应性描述符,而分子静电位和 Fukui 函数则有助于确定磺酰胺类化合物中的反应位点。为了深入了解超分子排列,我们进行了分子拓扑分析,包括 Hirshfeld 表面和分子中原子的量子理论。这些分析表明,各晶体中的分子间相互作用主要是闭壳作用,以范德华力和氢键为特征。此外,这些相互作用的稳定性也通过自然键轨道计算得到了证实。此外,我们还针对乙酰乳酸合成酶进行了毒力建模,以确定潜在的相互作用基团。我们还进行了分子对接研究,以检验磺胺类药物与酶结合位点的相互作用。利用分子中原子的量子理论,深入了解了毒性基团与存在于酶结合部位的氨基酸横向链之间相互作用的性质。对人类乙醚相关基因抑制、AMES 毒性、鱼类毒性、四膜虫毒性和蜜蜂毒性的测试表明,磺酰胺衍生物不会对这些物种产生毒性,而且可能具有良好的环境耐受性。这项研究的结果表明,有必要进行生物测试,以验证磺胺类药物的除草潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Structural-based analysis of sulfonamide derivatives: from solid states to acetolactate synthase enzyme interactions

Structural-based analysis of sulfonamide derivatives: from solid states to acetolactate synthase enzyme interactions

The discovery of non-toxic compounds with herbicidal activity remains a significant challenge in agricultural weed management practices. In this study, we conducted a comparative analysis of sulfonamide derivatives, namely sulfadiazine, sulfamerazine, and sulfamethazine, which are commonly used as antibiotic drugs. Our aim was to understand the impact of the –CH3 substituent group on the pyrimidine ring and its potential as herbicide candidates. We examined the geometric and electronic structures using density functional theory with the M06-2X hybrid exchange–correlation functional, coupled with the 6-311++G(d, p) basis set, in the gas phase. These geometric parameters were then compared to crystallographic data for validation. The frontier molecular orbital energies were employed to predict chemical reactivity descriptors, while molecular electrostatic potentials and Fukui functions aided in identifying the reactive sites within the sulfonamides. To gain insights into the supramolecular arrangement, we conducted molecular topology analyses, including the Hirshfeld surface and quantum theory of atoms in molecules. These analyses revealed that the intermolecular interactions in the respective crystals are primarily closed-shell, characterized as van der Waals forces and hydrogen bonds. Additionally, the stability of these interactions was confirmed through natural bond orbital calculations. Furthermore, we carried out toxicophoric modeling against the acetolactate synthase enzyme to identify potential interacting groups. Molecular docking studies were carried out to examine the interactions of sulfonamides with the enzyme's binding site. The quantum theory of atoms in molecules was employed to gain insights into the nature of interactions between the toxicophoric groups and the lateral chains of amino acids present at the enzyme's binding site. Tests of Human Ether-a-go-go-Related Gene Inhibition, AMES Toxicity, Fish Toxicity, Tetrahymena Pyriformis toxicity, and honey bee toxicity showed that the sulfonamide derivatives do not cause toxicity in these species and may present good environmental tolerance. The results obtained in this study suggest the need for biological tests to validate the herbicidal potential of sulfonamides.

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来源期刊
Rendiconti Lincei-Scienze Fisiche E Naturali
Rendiconti Lincei-Scienze Fisiche E Naturali MULTIDISCIPLINARY SCIENCES-
CiteScore
4.10
自引率
10.00%
发文量
70
审稿时长
>12 weeks
期刊介绍: Rendiconti is the interdisciplinary scientific journal of the Accademia dei Lincei, the Italian National Academy, situated in Rome, which publishes original articles in the fi elds of geosciences, envi ronmental sciences, and biological and biomedi cal sciences. Particular interest is accorded to papers dealing with modern trends in the natural sciences, with interdisciplinary relationships and with the roots and historical development of these disciplines.
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