Synthesis, antibacterial and antioxidant activities of Thiazole-based Schiff base derivatives: a combined experimental and computational study

Abstract

Background Thiazole-based Schiff base compounds display significant pharmacological potential with an ability to modulate the activity of many enzymes involved in metabolism. They also demonstrated to have antibacterial, antifungal, anti-inflammatory, antioxidant, and antiproliferative activities. In this work, conventional and green approaches using ZnO nanoparticles as catalyst were used to synthesize thiazole-based Schiff base compounds. Results Among the synthesized compounds, 11 showed good activities towards Gram-negative E. coli (14.40 ± 0.04), and Gram-positive S. aureus (15.00 ± 0.01 mm), respectively, at 200 μg/mL compared to amoxicillin (18.00 ± 0.01 mm and 17.00 ± 0.04). Compounds 7 and 9 displayed better DPPH radical scavenging potency with IC50 values of 3.6 and 3.65 μg/mL, respectively, compared to ascorbic acid (3.91 μg/mL). The binding affinity of the synthesized compounds against DNA gyrase B is within − 7.5 to − 6.0 kcal/mol, compared to amoxicillin (− 6.1 kcal/mol). The highest binding affinity was achieved for compounds 9 and 11 (− 6.9, and − 7.5 kcal/mol, respectively). Compounds 7 and 9 displayed the binding affinity values of − 5.3 to − 5.2 kcal/mol, respectively, against human peroxiredoxin 5. These values are higher than that of ascorbic acid (− 4.9 kcal/mol), in good agreement with the experimental findings. In silico cytotoxicity predictions showed that the synthesized compounds Lethal Dose (LD50) value are class three (50 ≤ LD50 ≤ 300), indicating that the compounds could be categorized under toxic class. Density functional theory calculations showed that the synthesized compounds have small band gap energies ranging from 1.795 to 2.242 eV, demonstrating that the compounds have good reactivities. Conclusions The synthesized compounds showed moderate to high antibacterial and antioxidant activities. The in vitro antibacterial activity and molecular docking analysis showed that compound 11 is a promising antibacterial therapeutics agent against E. coli, whereas compounds 7 and 9 were found to be promising antioxidant agents. Moreover, the green synthesis approach using ZnO nanoparticles as catalyst was found to be a very efficient method to synthesize biologically active compounds compared to the conventional method.

Cytotoxic mixed-ligand complexes of Cu(II): A combined experimental and computational study

“…The molecular docking studies of the compounds ( 1 and 2 ) and the positive control (cisplatin) were performed using the AutoDock 4.2.6 software ( Allouche, 2011 ). The same protocols to our previous works were used ( Bitew et al, 2021 ; Lemilemu et al, 2021 ; Damena et al, 2022 ). Briefly, the PDB file for ERα was downloaded from the Protein Data Bank with a resolution of 2.4 Å ( Xie et al, 2017 ).…”

“…The synthesized metal complexes and the ligands were subjected for physicochemical and pharmacokinetic (ADME) evaluation using SwissADME ( Daina et al, 2017 ). The protocol to predict physicochemical properties, pharmacokinetic and drug likeness evaluation, and BOILED egg model of the metal complexes and the ligands were conducted according to our previous work ( Bitew et al, 2021 ; Lemilemu et al, 2021 ; Damena et al, 2022 ).…”

Novel Zinc(II) and Copper(II) Complexes of 2-((2-Hydroxyethyl)amino)quinoline-3-carbaldehyde for Antibacterial and Antioxidant Activities: A Combined Experimental, DFT, and Docking Studies

“… 51 This method has been used and gave results, which are in good agreement with the corresponding experimental results in our previous studies. 13 , 52 − 54 Methanol and the polarizable continuum model in its integral equation formalism (IEF-PCM) 55 were employed to mimic the experimental synthesis method and consider solvent effects. The same method and level of theory as that of the geometry optimizations was employed to calculate the frequencies and confirm that the optimized geometries are real minima.…”

ZnO Nanoparticle-Assisted Synthesis of Thiazolo[3,2-α]Pyrimidine Analogs: Antibacterial and Antioxidant Activity, In Silico Molecular Docking, and ADMET Prediction Study

“…Te thiazole moiety was synthesized by following the Hantzsch's modifed method. Te rapid and efcient solvent-free reaction of substituted acetophenones (1-3) derivatives with thiourea (8) and iodine under thermal conditions led to 2-Amino-4-arylthiazoles derivatives, 9-11 (S1 Figure 2), which were prepared as per literature protocol with slight modifcations [11,12]. [3,2-α] pyrimidine analogs in the presence of ZnO nanoparticles as a catalyst derived from chalcone (12)(13)(14)(15)(16)(17)(18)(19)(20).…”

“…Te rapid and efcient solvent-free reaction of substituted acetophenones (1-3) derivatives with thiourea (8) and iodine under thermal conditions led to 2-Amino-4-arylthiazoles derivatives, 9-11 (S1 Figure 2), which were prepared as per literature protocol with slight modifcations [11,12]. [3,2-α] pyrimidine analogs in the presence of ZnO nanoparticles as a catalyst derived from chalcone (12)(13)(14)(15)(16)(17)(18)(19)(20). A solution of substituted 2-amino-4-substituted phenylthiazole, 9-11 (1.5 mmol) in ethanol (20 mL) was mixed with the appropriate α, β-unsaturated ketones, 5-7 (1.5 mmol) in the presence of Na metal (0.5 g) under the use of ZnO nanoparticles as a catalyst (0.43 mg, 0.2 mmol, 20 mol %) as depicted in Scheme.…”