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

Yoseph Samuel,Ankita Garg,Endale Mulugeta,Saad Tayyab

doi:10.1155/2021/7534561

Yoseph Samuel, Ankita Garg + Show 2 more

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https://doi.org/10.1155/2021/7534561

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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.

Highlights

Most of the organic compounds including natural products possess heterocyclic rings as a core part of it, and they provide the ability to alter their molecular conformation, solubility, physicochemical, pharmaceutical, and biological activities. ese molecules perform remarkable functions in nature, medication, and innovation [1]
E synthesized compounds were characterized on the basis of physical and spectral analysis. e UV-Vis spectra of synthesized compounds were recorded on double-beam UV-Vis spectrophotometer using methanol as blank solvents for studying antioxidant activity. e 1H and 13C NMR spectra of the synthesized compounds were recorded on Bruker Avance 400 MHz NMR spectrophotometer using DMSO-d6 as the solvent, and the values are expressed in δ ppm
Compound 7 was reacted with benzene sulfonyl chloride/ toluene sulfonyl chloride in methanol and the mixture was basified by dry pyridine to afford compound 11a, 11b with 81%, and 72% yield, respectively [26]

Summary

Introduction

Most of the organic compounds including natural products possess heterocyclic rings as a core part of it, and they provide the ability to alter their molecular conformation, solubility, physicochemical, pharmaceutical, and biological activities. ese molecules perform remarkable functions in nature, medication, and innovation [1]. Most of the organic compounds including natural products possess heterocyclic rings as a core part of it, and they provide the ability to alter their molecular conformation, solubility, physicochemical, pharmaceutical, and biological activities. Organic compounds with ring system containing sulfur, nitrogen, and oxygen as heteroatom are proven to be potent bioactive agents [2]. One of the most important groups of organic compounds among fivemember heterocyclic compounds containing S and N atoms are called thiazoles and they belong to the group of azole heterocycles. Iazole is structurally similar to imidazole and oxazole with the thiazole sulfur replaced by nitrogen in imidazole and oxygen in oxazole, respectively [3]. Biochemistry Research International derived from sulfonamide by replacing one amide hydrogen atom with thiazole group. Sulfathiazole is the primary powerful bioactive agent efficiently utilized for the prevention and cure of bacterial infections

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