Synthesis, antimicrobial properties and in silico studies of aryloxyacetic acid derivatives with hydrazone or thiazolidine-4-one scaffold

Abstract

In this work, twenty hydrazide-hydrazone and 4-thiazolidinone derivatives were synthesized starting from m-cresol. Antimicrobial evaluation was carried out by microdilution method against Enterococcus faecalis and Staphylococcus aureus as Gram-positive bacteria and Escherichia coli and Pseudomonas aeruginosa as Gram-negative bacteria, and three pathogenic fungi Candida albicans, Candida parapsilosis and Candida krusei. Some compounds possessed considerable antimicrobial properties against the tested microorganisms, particularly against E. coli. 4-Thiazolidinones containing 3-methoxyphenyl and 3,5-dichlorophenyl moieties (4h and 4i) were found to be the most active derivatives with MICs of 2 μg/mL against E. coli. N'-[(3,5-dichlorophenyl)methylidene]-2-(3-methylphenoxy)acetohydrazide (3i) also displayed antifungal activity against Candida krusei that was comparable to fluconazole. Calculated drug-likeness and ADMET parameters of the most active compounds confirmed their potential as antimicrobial drug candidates. Molecular docking investigations were carried out in the thiamine diphosphate-binding site of pyruvate dehydrogenase multienzyme complex E1 component (PDHc-E1) to clarify the potential antibacterial mechanism against E. coli. The results showed the potential and importance of developing new hydrazones and 4-thiazolidinones that would be effective against microbial strains.

Communicated by Ramaswamy H. Sarma

Keywords:

• Cresol
• hydrazone
• 4-thiazolidinone
• molecular docking
• antimicrobial activity

Acknowledgements

We thank Dr. Esen Bellur Atıcı from Deva Holding A.Ş. (Turkey), for her generous help on obtaining ¹³C-NMR spectra of the synthesized compounds. MGG also would like to thank Prof. Dr. Gerhard Wolber (Freie Universität Berlin) for supplying the LigandScout 4.4. license.

Disclosure statement

No potential conflict of interest was reported by the authors

Funding

The author(s) reported there is no funding associated with the work featured in this article.

Data availability statement

The data that supports the findings of this work are available in the supplementary material.