Design and synthesis of novel 2,3,4-trisubstituted thiazole derivatives as preservative agents by in vitro and in silico approaches

KAYA A. Z., EVREN A. E., BAYSAL M., GÜL Ü. D., YURTTAŞ L.

Food Chemistry, vol.505, 2026 (SCI-Expanded, Scopus) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 505
  • Publication Date: 2026
  • Doi Number: 10.1016/j.foodchem.2026.148072
  • Journal Name: Food Chemistry
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, Chimica, Compendex, EMBASE, MEDLINE
  • Keywords: Antimicrobial activity, Ergosterol, Hydrazone, Molecular modeling, Preservative additives, Thiazole
  • Anadolu University Affiliated: Yes

Abstract

Today, there is an urgent need for new molecules because of the increasing development of fungal resistance. Here, novel phenol–thiazole–hydrazone hybrids were designed and synthesized using a mimic-to approach referenced from azole antifungals. After structural confirmation, the compounds were tested against fungi and further evaluated against the NIH/3T3 cells to determine their selectivity index as well as potential genotoxicity. All compounds have inhibitory activity against C. glabrata except 3a , while 3o inhibits C. albicans among others. Inhibition effects on NIH/3T3 cells indicated that 3o had the strongest cytotoxic effect, while 3 h had the least significant toxicity. Scanning-electron-microscope (SEM) analyses indicated that active compounds compromise cell integrity, thereby leading to cell death. The binding modes of lanestrol-demethylase (LDM)– 3o /− 3j complexes were investigated through in silico analysis, and structure–activity relationships (SAR) were established. Compounds 3b , 3g , 3i , 3j , 3k , and 3o are identified as potential preservative agents.