Synthesis, characterization, DFT, antioxidant, antibacterial, pharmacokinetics and inhibition of SARS-CoV-2 main protease of some heterocyclic hydrazones

Lilia Adjissi; Nadjib Chafai; Khalissa Benbouguerra; Imene Kirouani; Abdelkader Hellal; Houdheifa Layaida; Meriem Elkolli; Chawki Bensouici; Salah Chafaa

doi:10.1016/j.molstruc.2022.134005

Synthesis, characterization, DFT, antioxidant, antibacterial, pharmacokinetics and inhibition of SARS-CoV-2 main protease of some heterocyclic hydrazones

J Mol Struct. 2022 Dec 15:1270:134005. doi: 10.1016/j.molstruc.2022.134005. Epub 2022 Aug 23.

Authors

Lilia Adjissi¹, Nadjib Chafai¹, Khalissa Benbouguerra¹, Imene Kirouani¹, Abdelkader Hellal¹, Houdheifa Layaida¹, Meriem Elkolli², Chawki Bensouici³, Salah Chafaa¹

Affiliations

¹ Laboratory of Electrochemistry of Molecular Materials and Complex (LEMMC). Department of Process Engineering, Faculty of Technology, University of Ferhat ABBAS Setif-1, El-Mabouda campus, 19000 Sétif, Algeria.
² Laboratory of applied microbiology, Faculty of Natural and Life Sciences, University of Setif 1, Algeria.
³ Centre de Recherche en Biotechnologie, Ali Mendjli, Nouvelle Ville UV 03, BP E73 Constantine, Algeria.

Abstract

Three hydrazone derivatives have been synthesized using condensation reaction of 4-hydrazinylbenzoic acid with three aromatic aldehydes namely: thiophene-2-carbaldehyde, thiophene-3-carbaldehyde and 2-furaldehyde in ethanol at 78 °C reflux. The synthesized molecules have been characterized using spectroscopic and physicochemical methods including UV-Vis, IR, ¹H NMR, ¹³C NMR, ¹⁵N NMR and melting point determination. Optimized molecular structures, UV-Vis and IR spectra modeling, the reactivity, the stability and some quantum chemical parameters of the synthesized molecules were modeled utilizing density functional theory (DFT). The obtained theoretical results were found in good agreement with the experimental results. On the other hand, the antioxidant and antibacterial activities of the molecules under study were evaluated to better understand the associated mechanisms of action specifically. Also, predicted ADME-T and pharmacokinetic parameters indicated that these compounds showed good oral bioavailability. Finally, molecular docking has been used to predict the inhibitory activity of the studied hydrazone derivatives on the SARS-CoV-2 main protease (Mpro).

Keywords: Antibacterial; Antioxidant; DFT; Hydrazones; SARS-CoV-2; Synthesis.