Synthesis, structural and spectroscopic characterization, in silico study, and antinociceptive effect in adult zebrafish of 2-(4-isobutylphenyl) -N'-phenylpropanohydrazide

• Published in: Journal of molecular structure 2021-11, Vol.1243, p.130860, Article 130860
• Main Authors: Garcia, Tatiana Rodrigues, Freire, Paulo de Tarso Cavalcante, Bandeira, Paulo Nogueira, de Sousa, Amanda Pereira, Julião, Murilo Sérgio da Silva, Rodrigues, Tigressa Helena Soares, Marinho, Márcia Machado, Marinho, Emmanuel Silva, Almeida-Neto, Francisco Wagner Queiroz, Ferreira, Maria Kueirislene Amâncio, da Silva, Antonio Wlisses, de Menezes, Jane Eire Silva Alencar, de Paiva, Aldeneide Soares, da Hora, João Pedro, Barreto, Antônio César Honorato, dos Santos, Hélcio Silva, Teixeira, Alexandre Magno Rodrigues
• Format: Article
• Language: English
• Subjects: ADMET; Ibuprofen derivative; Molecular docking; UV-Vis; Vibrational spectroscopy
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2021.130860

•Structural characterization of a novel ibuprofen derivative.•Vibrational analysis was carried out.•Electronic absorption spectrum was obtained.•Molecular docking and ADMET studies were carried out.•The novel compound was not toxic, and affected locomotor activity of the Zebrafish. In this work, an ibuprofen derivative 2-(4-isobutylphenyl) -N'-phenylpropanohydrazide (ACPHZN) was synthesized and characterized by NMR, ATR-FTIR, FT-Raman, and UV-Vis spectroscopy, while their structural and spectroscopic properties were investigated using DFT calculations. In vivo study using animal model in an adult Zebrafish (Danio rerio), and molecular docking was performed. In addition, molecular descriptors of the properties of absorption, distribution, metabolism and excretion, and toxicity (ADMET) were obtained. The data calculated for ibuprofen derivative are in accordance with the experimental values. From the assays in adult zebrafish, it was found that the ibuprofen derivative was non-toxic and exhibited analgesic properties through the TRPA1, TRPV1 and TRPM8 channels. Molecular docking revealed six interactions of ACPHZN with residues of the capsaicin binding site, and a more favorable affinity energy (-9.0 kcal / mol). ADMET studies suggest that ACPHZN has a pharmacological principle as an oral drug based on a longer half-life in the human body. [Display omitted]