Synthesis, DFT Analysis, and Evaluation of Antibacterial and Antioxidant Activities of Sulfathiazole Derivatives Combined with In Silico Molecular Docking and ADMET Predictions

Abstract

Synthetic modifications of sulfathiazole derivatives become an interesting approach to enhance their biological properties in line with their applications. As a result, sulfathiazole derivatives become a good candidate and potential class of organic compounds to play an important role towards medicinal chemistry. In present study, one thiazole derivative and two new sulfathiazole derivatives are synthesized with 94% and 72–81% yields, respectively. Furthermore, the synthesized compounds were evaluated for their in vitro antibacterial activity against two Gram-negative (E. coli and P. aeruginosa) and two Gram-positive bacterial strains (S. pyogenes and S. aureus) by disk diffusion method. Among synthesized compounds, compound 11a showed potent inhibitory activity against Gram-negative, E. coli with 11.6 ± 0.283 mm zone of inhibition compared to standard drug sulfamethoxazole (15.7 ± 0.707 mm) at 50 mg/mL. The radical scavenging activities of these compounds were evaluated using DPPH radical assay, and compound 11a showed the strongest activity with IC50 values of 1.655 μg/mL. The synthesized compounds were evaluated for their in silico molecular docking analysis using S. aureus gyrase (PDB ID: 2XCT) and human myeloperoxidase (PDB ID: 1DNU) and were found to have minimum binding energy ranging from −7.8 to −10.0 kcal/mol with 2XCT and −7.5 to −9.7 with 1DNU. Compound 11a showed very good binding score −9.7 kcal/mol with both of the proteins and had promising alignment with in vitro results. Compound 11b also showed high binding scores with both proteins. Drug likeness and ADMET of synthesized compounds were predicted. The DFT analysis of synthesized compounds was performed using Gaussian 09 and visualized through Gauss view 6.0. The structural coordinates of the lead compounds were optimized using B3LYP/6–31 G (d,p) level basis set without any symmetrical constraints. Studies revealed that all the synthesized compounds might be candidates for further antibacterial and antioxidant studies.

WITHDRAWN: Synthesis, characterization and computational studies of 2-amino-4-substituted thiazoles, their divalent nickel and cobalt complexes and molecular docking studies of their ligands as potent μ-opioid receptor agonists

“…The thiazole ring is a structural component of natural compounds such as Vitamin B 1 , penicillin and carboxylase (Maupin-Furlow, 2018). In addition, drugs containing sulfathiazole, phthalylsulfatiazole and their derivatives (such as famotidine, thiabendazole, epothilone and meloxicam) are frequently used in human medicine (Dawood et al, 2021;Samuel et al, 2021;Yurttaş et al, 2021). An interesting use of thiazoles has been reported by Stangeland and Sammakia (2004) in the halogen dance reaction for the total synthesis of WS75624 B.…”

Clustering Analysis, Structure Fingerprint Analysis, and Quantum Chemical Calculations of Compounds from Essential Oils of Sunflower (Helianthus annuus L.) Receptacles

“…The quantum chemical calculations were carried out using the B3LYP function [ 40 , 41 , 42 , 43 ] implemented in the Gaussian 09 program at the 6–31 G* set [ 44 , 45 ]. Frequency calculations were performed to obtain free energy corrections at 298.15 K and 1atm pressure.…”

Controlled synthesis of spinous gold nanoparticles and their use for surface-enhanced Raman scattering (SERS) detection of the antibiotic sulfathiazole

“…As broad spectrum antibiotics for treating human and animal bacterial infections, 1,2 sulfonamides are commonly used in pharmacological medicine, 3 veterinary, 4 agriculture, and aquaculture because of their high efficacy and low cost. 5,6 However, the disproportionate use of sulfonamides leads to residue contamination in organisms and the natural environment and causes various unfavourable adverse reactions such as digestive and respiratory diseases. 7 Using large doses of sulfonamides may cause severe allergic reactions related to Stevens-Johnson syndrome and toxic epidermal necrolysis.…”

“…20 Also, several theoretical studies have been performed to validate the structures and energetics, along with the electronic and spectroscopic features of STZ and its derivatives as well. 6,26 However, there still exist many intrinsic limitations associated with these efforts. Indeed, the binding modes, energetic properties, and the SERS chemical enhancement of such a sulfa drug by Au nanoparticles still need to be fully elucidated.…”