Synthesis, X-ray Single Crystal Structure, Molecular Docking and DFT Computations on N-[(1E)-1-(2H-1,3-Benzodioxol-5-yl)-3-(1H-imidazol-1-yl)propylidene]-hydroxylamine: A New Potential Antifungal Agent Precursor
Mycoses are serious health problem, especially in immunocompromised individuals. A new imidazole-bearing compound containing an oxime functionality was synthesized and characterized with different spectroscopic techniques to be used for the preparation of new antifungal agents. The stereochemistry of the oxime double bond was unequivocally determined via the single crystal X-ray technique. The title compound 4, C 13 H 13 N 3 O 3 ·C 3 H 8 O, crystallizes in the monoclinic space group P2 1 with a
... e group P2 1 with a = 9.0963(3) Å, b = 14.7244(6) Å, c = 10.7035(4) Å, β = 94.298 (3) • , V = 1429.57(9) Å 3 , Z = 2. The molecules were packed in the crystal structure by eight intermolecular hydrogen bond interactions. A comprehensive spectral analysis of the title molecule 4 has been performed based on the scaled quantum mechanical (SQM) force field obtained by density-functional theory (DFT) calculations. A molecular docking study illustrated the binding mode of the title compound 4 into its target protein. The preliminary antifungal activity of the title compound 4 was determined using a broth microdilution assay. Molecules 2017, 22, 373 2 of 17 this serious problem, the development of new alternative antifungal drug therapies with improved efficacy, broader activity and favorable safety profile has attracted a great deal of interest [3, 4] . Azole-based compounds having either an imidazole or triazole pharmacophore moiety in their structure, constitute the mainstay of the antifungal chemotherapeutic agents used in the clinic [5, 6] . Azoles competitively inhibit cytochrome P450-dependent lanosterol 14α-demethylase (CYP51) resulting in depletion of ergosterol in fungi making them unable to grow in a normal way [7, 8] . A screening the literature revealed that most of the available imidazole-bearing antifungal agents have two carbon spacers between the imidazole moiety and an aromatic residue, while few antifungals have a three carbon spacer between the pharmacophore and the aromatic part    . On the other hand, the benzodioxole moiety is found in a sizable number of biologically active compounds with a wide range of activities      . The title molecule features both the 1,3-benzodioxole moiety and the imidazole nucleus connecting to each other through a three carbon bridge. Therefore, the current investigation deals with the synthesis, molecular characterization and single crystal X-ray structure of a new oxime derivative, namely N-[(1E)-1-(2H-1,3-benzodioxol-5-yl)-3-(1H-imidazol-1yl)propylidene]hydroxylamine (4) to be utilized as a potential precursor for imidazole-bearing antifungal agents. The stereochemistry of the imine functionality in the title molecule 4 was certainly determined via the single crystal X-ray crystallography technique. In addition, density-functional theory (DFT) computations were also performed as a useful tool to investigate the electronic structure and molecular geometry of the title molecule 4. Molecular docking studies were conducted in order to predict the biological activity of compound 4.