Synthesis, Spectroscopic Characterization, Antibacterial Activity, and Computational Studies of Novel Pyridazinone Derivatives

Abstract

In this work, a novel series of pyridazinone derivatives (3–17) were synthesized and characterized by NMR (1H and 13C), FT-IR spectroscopies, and ESI-MS methods. All synthesized compounds were screened for their antibacterial activities against Staphylococcus aureus (Methicillin-resistant), Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, and Acinetobacter baumannii. Among the series, compounds 7 and 13 were found to be active against S. aureus (MRSA), P. aeruginosa, and A. baumannii with the lowest MIC value range of 3.74–8.92 µM. Afterwards, DFT calculations of B3LYP/6-31++G(d,p) level were carried out to investigate geometry structures, frontier molecular orbital, molecular electrostatic potential maps, and gap energies of the synthesized compounds. In addition, the activities of these compounds against various bacterial proteins were compared with molecular-docking calculations. Finally, ADMET studies were performed to investigate the possibility of using of the target compounds as drugs.

Synthesis of 1,3‐Disubtitituted Tetrahydropyrimidinium Salts and Determination of Their Biological Properties and Molecular Docking

“…These computations are utilized to study the interactions between substances and proteins. The parameter of docking score for molecules, which determines the results of this parameter is the interactions, which occur between proteins and molecules, is the most crucial factor used when comparing molecule activities in molecular docking calculations [40] . Chemical interactions include polar and hydrophobic contacts, hydrogen bonds, and halogen interactions [41] .…”

“…The parameter of docking score for molecules, which determines the results of this parameter is the interactions, which occur between proteins and molecules, is the most crucial factor used when comparing molecule activities in molecular docking calculations. [40] Chemical interactions include polar and hydrophobic contacts, hydrogen bonds, and halogen interactions. [41] It is well recognized that as these significant interactions multiply, so do the activities of molecules.…”

Synthesis, Characterization and Cytotoxic Evaluation of New Pyrrolo[1,2-b]pyridazines Obtained via Mesoionic Oxazolo-Pyridazinones

“…), in various drugs (e.g., sunitinib, atorvastatin, zomepirac, tolmetin) (Figure 1) and in numerous bioactive compounds with a wide spectrum of biological properties including antitumor action, is well known [4,5]. Sixmembered heterocycles with pyridazine core are other natural or synthetic compounds, being a privileged scaffold in the development of new drugs, some of them being already marketed, such as tepotinib, pildralazine, cadralazine, emorfazone, minaprine (Figure 1) [6][7][8]. The interest in heterocyclic condensed systems with bridgehead nitrogen from pyrroloazines class has been growing for several decades, both for the versatility of their chemistry and especially for their pharmaceutical potential.…”

“…The cycloaddition reactions of the mesoionic münchnones is a chosen method in the synthesis of the compounds from these classes, this procedure has been applied by Dumitrascu et al [32,33] for a new synthesis of pyrrolo [1,2-b]pyridazine derivatives, starting from 3(2H)pyridazinone acids. The pyridazinone skeleton is also present in many compounds with significant biological activities including anticancer, antiinflammatory, analgesic, antimicrobial, antidiabetic, anticonvulsant, anxiolytic, antidepressant, antihypertensive [7,8,[34][35][36][37], and optical properties [38,39]. The interest in heterocyclic condensed systems with bridgehead nitrogen from pyrroloazines class has been growing for several decades, both for the versatility of their chemistry and especially for their pharmaceutical potential.…”

Exploring Three Avenues: Chemo- and Regioselective Transformations of 1,2,4-Triketone Analogs into Pyrazoles and Pyridazinones

“…At the same time, pyridazine derivatives have attracted extensive attention due to their broad spectrum of biological activity, which has found use in therapeutic agents for the treatment of vasoconstriction (levosimendan [ 26 ]), allergies (azelastine [ 27 ]), cancer (olaparib [ 28 ]), and depression (minaprine [ 29 ]). In particular, pyridazinone scaffold is considered crucial for the discovery of drugs [ 11 , 14 , 30 , 31 , 32 , 33 , 34 , 35 ].…”