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Volume 21, Issue 13
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

Background

Novel antibiotics are needed to stem the rise of antimicrobial resistance. N-Methyl-2-phenylmaleimide (NMP) compounds previously synthesised by our research group are structural analogues of 2,3,5-substituted perhydropyrrolo[3,4-]isoxazole-4,6-diones found by others to have antibacterial activity.

Objectives

This study aims to explain the significance of NMPs and their antibacterial activity. The antibacterial activity of the NMPs was determined against , , , and . The partition coefficient of the NMPs and a pharmacophore model were used to explain their antibacterial activity.

Methods

The Kirby Bauer Disc diffusion method was used to screen the NMPs for activity, while the broth microdilution method was used to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the active NMPs. Using the antibacterial activity of 2,3,5-substituted perhydropyrrolo[3,4-]isoxazole-4,6-diones, a common feature pharmacophore model was constructed and validated. The rank score, fit value, enrichment factor (EF20%), and receiver operating characteristic area under the curve (ROC-AUC) were used as validation metrics.

Results

The NMPs were only active against , with compound (4 µg/ml) being the most active. The majority of NMPs were bacteriostatic. A common feature pharmacophore model was validated (rank score: 120.5; fit value: 4; EF20%: 4.3; ROC-AUC: 0.9 ± 0.03) and showed that three hydrogen bond acceptors and a ring aromatic region are important for activity. Comparing the partition coefficient of the NMPs to their MIC a statistically significant correlation was found.

Conclusion

NMPs can be used as lead compounds in future studies. The validated pharmacophore model and partition coefficient can be used to develop more active compounds.

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2025-06-30

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In vitro and In silico Antibacterial Evaluation of N-Methyl-2-phenylmaleimides
Letters in Drug Design & Discovery 21, 2497 (2024); https://doi.org/10.2174/1570180820666230731144315
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  • Article Type:     Letter
Keyword(s): antibacterial activity; common feature pharmacophore modelling; Discovery studio; maleimide; minimum bactericidal concentration; minimum inhibitory concentration

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