Synthesis, Single Crystal X-ray Analysis, and Antifungal Profiling of Certain New Oximino Ethers Bearing Imidazole Nuclei

Abstract

Fungal infections threaten human health, particularly in immune-compromised patients worldwide. Although there are a large number of antifungal agents available, the desired clinical attributes for the treatment of fungal infections have not yet been achieved. Azoles are the mainstay class of the clinically used antifungal agents. In the current study, the synthesis, spectroscopic characterization, and antifungal activity of certain new oximino ethers Va–n bearing imidazole nuclei are reported. The (E)-configuration of the imine double bond of the synthesized compounds Va–n has been confirmed via single crystal X-ray analysis of compound Vi as a representative example of this class of compounds. The molecular structure of compound Vi was crystallized in the monoclinic, P21/c, a = 18.7879(14) Å, b = 5.8944(4) Å, c = 16.7621(12) Å, β = 93.063(3)°, V = 1855.5(2) Å3, Z = 4. The in vitro antifungal activity of the synthesized compounds Va–n were evaluated using diameter of the inhibition zone (DIZ) and minimum inhibitory concentration (MIC) assays against different fungal strains. Compound Ve manifested anti-Candida albicans activity with an MIC value of 0.050 µmol/mL, being almost equipotent with the reference antifungal drug fluconazole (FLC),while compounds Vi and Vn are the most active congeners against Candida parapsilosis, being equipotent and about twenty-three times more potent than FLC with an MIC value of 0.002 µmol/mL. The results of the current report might support the development of new potent and safer antifungal azoles.

Synthesis and Spectroscopic Identification of Certain Imidazole-Semicarbazone Conjugates Bearing Benzodioxole Moieties: New Antifungal Agents

“…The title compounds 5a – o were evaluated for their in vitro antifungal activity using diameter of the inhibition zone (DIZ) and minimum inhibitory concentration (MIC) assays against Candida albicans , Candida tropicalis and Aspergillus niger according to the literature protocols [25].…”

(2E)-2-[1-(1,3-Benzodioxol-5-yl)-3-(1H-imidazol-1-yl)propylidene]-N-(2-chlorophenyl)hydrazine carboxamide: Synthesis, X-ray Structure, Hirshfeld Surface Analysis, DFT Calculations, Molecular Docking and Antifungal Profile

“…The MICs of the semicarbazone 4 towards various fungal strains were inspected according to literature method [20].…”

“…In a continuation of our efforts to obtain new potent antifungal compounds [18][19][20][21][22], we were inspired to design and synthesize (2E)-2-[1-(1,3-benzodioxol-5-yl)-3-(1H-imidazol-1-yl) propylidene]-N-(2-chlorophenyl)hydrazinecarboxamide to be examined as a new antifungal agent. The title compound comprises three pharmacophore parts, namely imidazole, semicarbazone, and benzodioxole with a three-carbon bridge separating benzodioxole and imidazole fragments with the aim to get new potent drug-like antifungal hybrid.…”