Synthesis, Characterization, Molecular Docking, ADMET Study, and Antimicrobial Evaluation of New Mannich Bases of Isatin–Thiazole Imine Bases

Marwa Hashim Al-Musawi; May Mohammed Jawad Al-Mudhafar

doi:10.54133/ajms.v6i2.835

Authors

Marwa Hashim Al-Musawi Department of Pharmaceutical Chemistry, College of Pharmacy, University of Baghdad, Baghdad, Iraq https://orcid.org/0009-0005-5516-0014
May Mohammed Jawad Al-Mudhafar Department of Pharmaceutical Chemistry, College of Pharmacy, University of Baghdad, Baghdad, Iraq https://orcid.org/0000-0002-9747-3140

DOI:

https://doi.org/10.54133/ajms.v6i2.835

Keywords:

2-aminothiazole, Antimicrobial activity, Isatin, Mannich bases

Abstract

Background: The isatin molecule is present in many natural substances, including plants and animals, and is used to prepare compounds with various biological activities. Objectives: To synthesize a new series of isatin derivatives with the expectation that they will have antimicrobial activity. Methods: Thiazole Schiff bases were synthesized from various Mannich bases of isatin to evaluate their antimicrobial properties. Initially, Mannich bases (2a–e) were synthesized by reacting isatin with formaldehyde and different secondary amines. Subsequently, they were treated with 2-aminothiazole to yield the final compounds (3a–e). Spectroscopic characterization was done via FT-IR and ¹H-NMR. The antimicrobial screening was conducted on all derivatives. Molecular docking and ADMET analysis were performed on the final compounds, comparing them with standard drugs (ciprofloxacin and fluconazole). Results: The antimicrobial activity was assessed on two Gram-positive bacteria, Staphylococcus aureus and Bacillus licheniformis; two Gram-negative bacteria, Escherichia coli and Acinetobacter baumannii; and one fungus species, Candida albicans. Molecular docking has recorded higher docking scores for 3d and 3e compared to ciprofloxacin and fluconazole. The virtually active molecules showed an adequate drug-like profile and desired pharmacokinetic properties in the ADMET analysis. Conclusions: Most derivatives displayed significant antimicrobial activity, with compound 3e being the most active, followed by compound 3b. Molecular docking revealed higher scores for compound 3e compared to fluconazole and for compounds 3d and 3e compared to ciprofloxacin. ADMET analysis of compound 3e showed excellent absorption, consistent with its strong GIT absorption.

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