ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

An experimental insight into a novel diethylamino isoniazid derivative organic single crystal for potential anxiolytic effect of in an adult zebrafish model with participation of serotonergic GABAA receptors

Antônio Mateus Gomes Pereira, Francisco Wagner Queiroz Almeida-Neto, Alejandro Pedro Ayala, Antônio César Honorato Barreto, Murilo Sérgio da Silva Julião, Aldeneide Soares de Paiva, Francisco Flavio da Silva Lopes, Emmanuel Silva Marinho, Jane Eire Silva Alencar de Menezes, Maria Kueirislene Amancio Ferreira, Jesyka Macedo Guedes, Alexandre Magno Rodrigues Teixeira, and Hélcio Silva dos Santos

Graduate Program in Biotechnology, Northeast Network of Biotechnology, State University of Ceará, Fortaleza, Brazil

E-mail: helciodossantos@gmail.com

Received: 30 January 2024  Accepted: 30 November 2024

Abstract:

In the present work we present a study of the structural, vibrational, electronic, and electrochemical properties of the hydrazone crystal (E)-N′-(4-(diethylamino)benzylidene)isonicotinohydrazide monohydrate (C₁₇H₂₀N₄O·H₂O, hereafter named HDZIETA monohydrate). The molecular structure of HDZIETA monohydrate was determined by Nuclear Magnetic Resonance and by single-crystal X-Ray Diffraction (XRD), and characterized by Fourier Transform Raman (FT-Raman), Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR), and Ultraviolet–visible (UV–Vis) spectroscopy, and by cyclic voltammetry. Theoretical calculations of quantum chemistry using the density functional theory method with the B3LYP/6-311 + + G(d,p) level of theory were carried out to compute the structural, vibrational, and global and local reactivity properties of this hydrazone. The HDZIETA monohydrate, at temperature of 150 K, has a monoclinic structure with P2₁/c space group, and four molecules per unit cell, with the following cell parameters: a = 14.2969(3) Å, b = 11.0539(2) Å, c = 10.9138(2) Å, and β = 105.6570(10)º. The crystalline structure is stabilized by intermolecular short contacts involving the water molecules of the unit cell. The ¹H NMR spectrum showed a doublet at δ_H 8.31 ppm for the hydrogen of the azomethine group (HC=N), which can be confirmed by the signal at δ_C 149.1 ppm in the ¹³C NMR spectrum. The UV–Vis spectrum revealed molecular absorption bands observed at 206 nm, 244 nm, 300 nm related to electronic transitions in the molecule. The cyclic voltammogram showed a single peak at E_pa = 0.838 V due to the irreversible oxidation of the azo group (= N–N) presents in the HDZIETA monohydrate molecule. The study indicated that HDZIETA caused anxiolytic behavior in the animals. This effect may occur through the interaction of this compound with the serotonergic receptors 5-HT1, 5-HT2A and 5-HT2c. ADME predictive tests based on MPO suggest that the substance presents a lipid-soluble balance that allows an alignment between high Papp and metabolic stability, although it presents a pre-systemic metabolism site, without having severe effects on oral bioavailability and safety due to activation metabolic.

Keywords: Hydrazone; NMR; XRD; Conformational analysis; Vibrational analysis; Anxiolytic behavior

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-024-03838-z

Chemical Papers 79 (2) 1045–1061 (2025)