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

Autor: Şenkardeş S; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Maltepe, Marmara University, Başıbüyük, İstanbul, Turkey., Kart D; Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Hacettepe University, Sıhhiye, Ankara, Turkey., Bebek B; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Maltepe, Marmara University, Başıbüyük, İstanbul, Turkey.; Deva Holding A.S., R & D Center, Cerkezkoy, Tekirdag, Turkey., Gündüz MG; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Sıhhiye, Ankara, Turkey., Küçükgüzel ŞG; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Fenerbahçe University, Ataşehir, İstanbul, Turkey.
Jazyk: angličtina
Zdroj: Journal of biomolecular structure & dynamics [J Biomol Struct Dyn] 2023 Sep-Oct; Vol. 41 (15), pp. 7421-7432. Date of Electronic Publication: 2022 Sep 14.
DOI: 10.1080/07391102.2022.2121761
Abstrakt: 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.
Databáze: MEDLINE