Synthesis, Molecular Docking, and Biological Evaluation of Novel Anthranilic Acid Hybrid and Its Diamides as Antispasmodics

新型邻氨基苯甲酸杂化物及其二酰胺的合成、分子对接及作为解痉药的生物学评价

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作者:Miglena Milusheva, Vera Gledacheva, Iliyana Stefanova, Mehran Feizi-Dehnayebi, Rositsa Mihaylova, Paraskev Nedialkov, Emiliya Cherneva, Yulian Tumbarski, Slava Tsoneva, Mina Todorova, Stoyanka Nikolova

Methods

Due to the predicted in silico methods spasmolytic activity, we synthesized a hybrid molecule of anthranilic acid and 2-(3-chlorophenyl)ethylamine. The obtained hybrid was then applied in acylation with different acyl chlorides. Using in silico analysis, pharmacodynamic profiles of the compounds were predicted. A thorough biological evaluation of the compounds was conducted assessing their in vitro antimicrobial, cytotoxic, anti-inflammatory activity, and ex vivo spasmolytic activity. Density functional theory (DFT) calculation, including geometry optimization, molecular electrostatic potential (MEP) surface, and HOMO-LUMO analysis for the synthesized compounds was conducted using the B3LYP/6-311G(d,p) method to explore the electronic behavior, reactive regions, and stability and chemical reactivity of the compounds. Furthermore, molecular docking simulation along with viscosity measurement indicated that the newly synthesized compounds interact with DNA via groove binding mode. The obtained

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