Synthesis, Characterization, and Molecular Docking Study of Some Novel Imidazole Derivatives as Potential Antifungal Agents


Isik A., ÇEVİK U. A., SAĞLIK B. N., ÖZKAY Y.

JOURNAL OF HETEROCYCLIC CHEMISTRY, vol.56, no.1, pp.142-152, 2019 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 56 Issue: 1
  • Publication Date: 2019
  • Doi Number: 10.1002/jhet.3388
  • Journal Name: JOURNAL OF HETEROCYCLIC CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.142-152
  • Eskisehir Osmangazi University Affiliated: No

Abstract

The azole pharmacophore is still regarded as a viable lead structure for the synthesis of more effective antifungal agents. In this study, two novel series of imidazole derivatives containing dithiocarbamate (5a-5g) and (benz)azolethiol (6a-6n) side chains that are structurally related to the famous antifungal azole pharmacophore were synthesized, and the structures of them were characterized by spectral (IR, H-1 NMR, C-13 NMR, and MS spectra) analyses. The synthesized compounds were screened in vitro antifungal activity against pathogenic strains fungi. Theoretical ADME (absorption, distribution, metabolism, and excretion) predictions were calculated for final compounds. A molecular docking study of the most active compound with target "lanosterol 14 alpha-demethylase" (CYP51) was performed to unravel the mode of antifungal action. Compound 5e, which features imidazole and 4-methoxybenzyl piperazine scaffolds, showed the most promising antifungal activity with an MIC50 value of 0.78 mu g/mL against C. krusei. Effect of the compound 5e against ergosterol biosynthesis was observed by LC-MS-MS method, which is based on quantification of ergosterol level in C. krusei.