Purpose The purpose of this study is the synthesis and structural characterization of 4-methyl-N-(pyrimidin-2-yl)benzenesulfonamide, along with In Vitro, and In Silico predictions of its biological properties. Methods In this study, 4-methyl-N-(pyrimidin-2-yl)benzenesulfonamide (1) was synthesized and characterized using FT-IR, 1H-NMR, CHNS, Melting point, and single-crystal X-ray diffraction. Hirshfeld surface for evaluating the intermolecular interactions in the crystal structure was determined by CrystalExplorer 17 software. In Vitro antibacterial activity was evaluated through well-diffusion agar and minimal inhibitory concentration methods. In silico molecular docking for three bacterial and fungal target proteins was performed using AutoDock Vina software. In Silico prediction of the median lethal dose was done using QSAR Toolbox 4.6, and the SwissADME database was also performed to assess the physicochemical properties. Results Antimicrobial analysis showed that 1 has potent antibacterial activity, with minimum inhibitory concentrations (MICs) of 125 mg/mL and 5 mg/mL for Bacillus subtilis and Staphylococcus aureus, respectively. Molecular docking studies also showed that this compound effectively binds to specific bacterial and fungal target proteins and exhibits high inhibitory activity. The results of molecular docking indicated the formation of hydrogen bonds between the ligand and the receptor under study with a free bond energy of -7.0, -6.6, and -6.4 kcal/mol. The analysis of Lipinski's rule showed that 1 had a bioavailability score of 0.55. Conclusion The results of this study indicate that 4-methyl-N-(pyrimidin-2-yl)benzenesulfonamide could be a lead compound for developing new antibacterial and antifungal drugs. Highlights<UnorderedList Mark="Bullet"> <ItemContent> 4-methyl-N-(pyrimidin-2-yl)benzenesulfonamide (1) has been synthesized and characterized. </ItemContent> <ItemContent> The Hirshfeld surface was used to investigate and quantify the intermolecular interactions. These results indicate a significant effect of hydrogen interactions and their role in the stability of the crystal lattice of 1. </ItemContent> <ItemContent> Antimicrobial properties of compound have been studied using the Agar well method and MIC techniques. </ItemContent> <ItemContent> Molecular docking studies were performed using four microbial and viral protein's active sites by AutoDock Vina software. </ItemContent> <ItemContent> The QSAR Toolbox software determined the median lethal dose. </ItemContent> <ItemContent> The pharmacokinetic properties were evaluated by the In Silico method. According to the RO5 prediction, 1 has high absorption through the digestive system. </ItemContent> <ItemContent> 4-methyl-N-(pyrimidin-2-yl)benzenesulfonamide could be a lead compound for developing antibacterial and antiviral drugs. </ItemContent> </UnorderedList> Graphical Abstract A novel 2-aminopyrimidine derivative, 4-methyl-N-(pyrimidin-2-yl)benzenesulfonamide (1), has been synthesized, and its biological properties have been determined. The antibacterial activity results evaluated 1 having significant activity on studied strains. In Silico molecular docking studies confirmed the appropriate activity of 1 on bacterial and fungal agents. Prediction of the bioavailability evaluation results confirmed this compound's biosafety.

Synthesis, Characterization and Biological Evaluation of a Sulfonamide-Based Antimicrobial Agent

期刊论文
发表日期：

2025年6月16日

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Aref Atefi,
Mohaddeseh Larypoor,
Masoumeh Tabatabaee,
Golnaz Bahramali

摘要

Purpose

The purpose of this study is the synthesis and structural characterization of 4-methyl-N-(pyrimidin-2-yl)benzenesulfonamide, along with In Vitro, and In Silico predictions of its biological properties.

Methods

In this study, 4-methyl-N-(pyrimidin-2-yl)benzenesulfonamide (1) was synthesized and characterized using FT-IR, ¹H-NMR, CHNS, Melting point, and single-crystal X-ray diffraction. Hirshfeld surface for evaluating the intermolecular interactions in the crystal structure was determined by CrystalExplorer 17 software. In Vitro antibacterial activity was evaluated through well-diffusion agar and minimal inhibitory concentration methods. In silico molecular docking for three bacterial and fungal target proteins was performed using AutoDock Vina software. In Silico prediction of the median lethal dose was done using QSAR Toolbox 4.6, and the SwissADME database was also performed to assess the physicochemical properties.

Results

Antimicrobial analysis showed that 1 has potent antibacterial activity, with minimum inhibitory concentrations (MICs) of 125 mg/mL and 5 mg/mL for Bacillus subtilis and Staphylococcus aureus, respectively. Molecular docking studies also showed that this compound effectively binds to specific bacterial and fungal target proteins and exhibits high inhibitory activity. The results of molecular docking indicated the formation of hydrogen bonds between the ligand and the receptor under study with a free bond energy of -7.0, -6.6, and -6.4 kcal/mol. The analysis of Lipinski's rule showed that 1 had a bioavailability score of 0.55.

Conclusion

The results of this study indicate that 4-methyl-N-(pyrimidin-2-yl)benzenesulfonamide could be a lead compound for developing new antibacterial and antifungal drugs.

Highlights

4-methyl-N-(pyrimidin-2-yl)benzenesulfonamide (1) has been synthesized and characterized.

The Hirshfeld surface was used to investigate and quantify the intermolecular interactions. These results indicate a significant effect of hydrogen interactions and their role in the stability of the crystal lattice of 1.

Antimicrobial properties of compound have been studied using the Agar well method and MIC techniques.

Molecular docking studies were performed using four microbial and viral protein's active sites by AutoDock Vina software.

The QSAR Toolbox software determined the median lethal dose.

The pharmacokinetic properties were evaluated by the In Silico method. According to the RO5 prediction, 1 has high absorption through the digestive system.

4-methyl-N-(pyrimidin-2-yl)benzenesulfonamide could be a lead compound for developing antibacterial and antiviral drugs.

Graphical Abstract

A novel 2-aminopyrimidine derivative, 4-methyl-N-(pyrimidin-2-yl)benzenesulfonamide (1), has been synthesized, and its biological properties have been determined. The antibacterial activity results evaluated 1 having significant activity on studied strains. In Silico molecular docking studies confirmed the appropriate activity of 1 on bacterial and fungal agents. Prediction of the bioavailability evaluation results confirmed this compound's biosafety.