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


ŞENKARDEŞ S., KART D., Bebek B., GÜNDÜZ M. G. , Kucukguzel S. G.

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 2022 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2022
  • Doi Number: 10.1080/07391102.2022.2121761
  • Journal Name: JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE
  • Keywords: Cresol, hydrazone, 4-thiazolidinone, molecular docking, antimicrobial activity, BIOLOGICAL-ACTIVITIES, DRUG DISCOVERY, E1 SUBUNIT, 4-THIAZOLIDINONES, LIPOPHILICITY, INHIBITION, BEHAVIOR, DESIGN
  • Hacettepe University Affiliated: Yes

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 mu g/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