Sustainable-green synthesis and antimicrobial screening of substituted 4,5-dihydropyrazole derivatives with computational docking insights

Green synthesis is crucial in organic chemistry because many industrial processes involve toxic chemicals and solvents that can significantly damage the environment. Green Chemistry wants to make synthetic procedures more effective and employ fewer harmful materials, reduce the number of steps in the synthetic routes, use fewer solvents and create as little waste as reasonably possible. In such way chemical synthesis will play a crucial role in advancing sustainable development.

Using a modified domestic microwave oven, a mixture of the corresponding chalcone and thiosemicarbazide was used to create 3,5-disubstituted-4,5-dihydropyrazole-l-carbothiamide. Synthesized compounds were characterised by using TLC and spectral data like FTIR, ¹H-NMR and Mass spectra and evaluated for antimicrobial activity. Molecular docking was carried out by using AutoDock Vina 1.5.7 software against S. aureus biotin protein ligase (PDB ID: 3V7R). SWISSADME and pkCSM database were used for an investigation of their ADMET properties.

The preparation of 4,5-dihydropyrazole derivatives with excellent yields was achieved by the green chemistry method of microwave-assisted technique. All the synthesised compounds revealed good antimicrobial activity against the pathogenic bacteria and fungi. Among all, compounds IIb and IIj exhibited good activity against E. coli and compound IIb, IIi and IIj was active against S. aureus whereas compound IId and IIj revealed promising activity against A. niger. In silico study demonstrated good docking score, excellent intestinal absorption, blood-brain barrier (BBB) permeability and complied with the Rule of Five. Toxicity testing revealed that none of the compounds caused cardiotoxicity, hepatotoxicity, AMES toxicity or skin sensitization as per the results predicted on the basis of ADMET study.

The results indicate that compound IIj showing good activity against E. Coli, S. aureus and A. niger could be lead compound for the development of antimicrobial agents.