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

• Published in: International journal of molecular sciences Vol. 24; no. 18; p. 13855
• Main Authors: Milusheva, Miglena, Gledacheva, Vera, Stefanova, Iliyana, Feizi-Dehnayebi, Mehran, Mihaylova, Rositsa, Nedialkov, Paraskev, Cherneva, Emiliya, Tumbarski, Yulian, Tsoneva, Slava, Todorova, Mina, Nikolova, Stoyanka
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.09.2023; MDPI
• Subjects: Acids; Acylation; anthranilic acid; Anti-inflammatory drugs; antimicrobial; antiproliferative; Bioavailability; Biological activity; Density functionals; DFT; hybrid molecules; in silico; Metabolism; Pharmaceutical industry; Pharmacokinetics; R&D; Research & development; Specific gravity; Bulgaria; Germany
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms241813855

The present article focuses on the synthesis and biological evaluation of a novel anthranilic acid hybrid and its diamides as antispasmodics. 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 results from all the experiments demonstrate that the hybrid molecule and its diamides inherit spasmolytic, antimicrobial, and anti-inflammatory capabilities, making them excellent candidates for future medications.