Benzenesulfonamide based 1,3,4-oxadiazole derivatives: synthesis, pharmacokinetic property prediction, bovine carbonic anhydrase activity and molecular docking studies

IF 2.1 3区 化学 Q3 CHEMISTRY, MULTIDISCIPLINARY
E. Alpınar , M. O. Kaya , Ö. Güleç , T. Demirci , Y. Kaya , M. Arslan
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引用次数: 0

Abstract

Sulphur-containing compounds are highly significant as they can possess a variety of biological activities that make them useful for pharmacological purposes and for the mechanism by which drugs such as antibiotics bind to and disrupt bacterial cell walls. In this study, novel thioalkyl substituted-1,3,4 oxadiazole-bearing sulfonamide compounds have been successfully synthesized and characterized by 1HNMR, 13CNMR, IR and elemental analysis. The effects of different thioalkyl groups on the 1,3,4 oxadiazole group, the IC50 value for Bovine Carbonic Anhydrase (BCA) found by in vitro, density functional theory (DFT) calculations, pharmacokinetics prediction and molecular docking are aimed to reveal the interactions on BCA. Firstly, pharmacokinetic predictions of thioalkyl substituted 1,3,4-oxadiazole compounds were generated to predict their potential hazards. Secondly, the predicted molecular docking data and 2D interaction were analyzed based on the best configuration from DFT optimization. Finally, the inhibition against BCA was analyzed in vitro and compared with the theoretical data. The compound (5o) has the best value such as IC50 = 51.80 µM, HOMO–LUMO (ΔE 4.488 Ev), ΔG −7.69 kcal/mol, Full fitness −2152.72 FF and predicted toxicity results showed no significant results except hepatotoxicity.

苯磺酰胺基 1,3,4-恶二唑衍生物:合成、药代动力学特性预测、牛碳酸酐酶活性和分子对接研究
含硫化合物具有多种生物活性,因此对药理学以及抗生素等药物与细菌细胞壁结合和破坏细菌细胞壁的机制非常有用,因此意义重大。本研究成功合成了新型硫代烷基取代的 1,3,4-噁二唑磺酰胺化合物,并通过 1HNMR、13CNMR、IR 和元素分析对其进行了表征。通过对 1,3,4-噁二唑基团上不同硫代烷基的影响、体外测定的牛碳酸酐酶(BCA)IC50 值、密度泛函理论(DFT)计算、药代动力学预测和分子对接,旨在揭示其与 BCA 的相互作用。首先,对硫代烷基取代的 1,3,4-恶二唑化合物进行药代动力学预测,以预测其潜在危害。其次,根据 DFT 优化的最佳构型分析了预测的分子对接数据和二维相互作用。最后,在体外分析了对 BCA 的抑制作用,并与理论数据进行了比较。化合物(5o)具有最佳值,如 IC50 = 51.80 µM、HOMO-LUMO (ΔE 4.488 Ev)、ΔG -7.69 kcal/mol、Full fitness -2152.72 FF,预测的毒性结果显示除肝毒性外无显著结果。
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来源期刊
Journal of Sulfur Chemistry
Journal of Sulfur Chemistry CHEMISTRY, MULTIDISCIPLINARY-
CiteScore
4.10
自引率
9.10%
发文量
38
审稿时长
6-12 weeks
期刊介绍: The Journal of Sulfur Chemistry is an international journal for the dissemination of scientific results in the rapidly expanding realm of sulfur chemistry. The journal publishes high quality reviews, full papers and communications in the following areas: organic and inorganic chemistry, industrial chemistry, materials and polymer chemistry, biological chemistry and interdisciplinary studies directly related to sulfur science. Papers outlining theoretical, physical, mechanistic or synthetic studies pertaining to sulfur chemistry are welcome. Hence the target audience is made up of academic and industrial chemists with peripheral or focused interests in sulfur chemistry. Manuscripts that truly define the aims of the journal include, but are not limited to, those that offer: a) innovative use of sulfur reagents; b) new synthetic approaches to sulfur-containing biomolecules, materials or organic and organometallic compounds; c) theoretical and physical studies that facilitate the understanding of sulfur structure, bonding or reactivity; d) catalytic, selective, synthetically useful or noteworthy transformations of sulfur containing molecules; e) industrial applications of sulfur chemistry; f) unique sulfur atom or molecule involvement in interfacial phenomena; g) descriptions of solid phase or combinatorial methods involving sulfur containing substrates. Submissions pertaining to related atoms such as selenium and tellurium are also welcome. Articles offering routine heterocycle formation through established reactions of sulfur containing substrates are outside the scope of the journal.
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