Qing-Guo Meng

Synthesis, Antifungal Activity, and Molecular Docking Studies of Novel Triazole Derivatives

In order to meet the urgent need for novel antifungal agents with improved activity and broader spectrum, a series of 3/4-[[N-alkyl-2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1, 2, 4-triazole)] propylamino] benzylethyl carbonate were designed, synthesized and evaluated as antifungal agents. The MIC80 values indicate that all the compounds showed only moderate or even no antifungal activities against nearly all the tested fungal pathogens. Moreover, the interactions of the most active compounds in the drug binding site of CACYP51 were also explored with the help of docking studies.

(3R,6R,12R,20S,24S)-20,24-Ep-oxy-dammarane-3,6,12,25-tetraol dihydrate.

The title compound, C30H52O5·2H2O, was degraded from pseudoginsenoside F11 which was extracted and seperated from Panax quinquefolium saponin. The three six-membered rings are in chair conformations. The five-membered ring is in an envelope conformation and the tetrahydrofuran ring has a conformation intermediate between half-chair and envelope. In the crystal, intermolecular O—H⋯O hydrogen bonds link molecules into a three-dimensional network. Intramolecular O—H⋯O hydrogen bonds also occur.

Synthesis and molecular docking studies of chrysin derivatives as antibacterial agents

In order to search for drugs with excellent antibacterial activities, a series of novel chrysin derivatives were designed, synthesized, and evaluated as antibacterial agents. Results of the preliminary antibacterial tests against six human pathogenic bacteria in vitro showed that these compounds exhibited activities to some extent, and some displayed excellent activities than the natural parent chrysin, while some were even more potent than the positive drug Penicillin. Moreover, the molecular model for the binding between compound 8c and the active site of Escherichia coli β-ketoacyl-acyl carrier protein synthase III (Escherichia coli FabH) was provided on the basis of the computational docking results.

(3R,6R,12R,20S,24R)-20,24-Ep­oxy­dammarane-3,6,12,25-tetra­ol

In the title compound, C30H52O5, the three six-membered rings are in chair conformations, the five-membered ring is in an envelope form and the tetrahydrofuran ring has a conformation intermediate between half-chair and sofa. Intramolecular O—H⋯O hydrogen bonds may influence the conformation of the molecule. In the crystal, molecules are linked by intermolecular O—H⋯O hydrogen bonds, forming a three-dimensional network.

Design, Synthesis andin vitroAntifungal Activities of Fluconazole Derivatives

In search of more effective antifungal agents, twenty-two new fluconazole derivatives containing 4-methyl phenol and thymine have been designed and synthesized based on the previous results of computer-aided drug design. All the derivatives retain the essential pharmacophore of fluconazole. Their structures are elucidated by 1 H NMR, elemental analysis and ESI-MS. Preliminary in vitro antifungal activities bioassay showed that compound 5l exhibits better in vitro antifungal activities against eight fungi except Aspergillus fumigatus (7544) than fluconazole, compounds 5a~5e, 5g, 5h, 7a and 7b show only moderate in vitro antifungal activities against different fungus. The introduction of propargyl group to nitrogen atom can enhance in vitro antifungal activities of this type derivative and it is worth of further research.

(3R,6R,12R,20S,24S)-3,6,12-Triacetyl-20,24-ep­oxy­dammarane-3,6,12,25-tetra­ol

The title compound, C36H58O8, was prepared from 20(S)-protopanaxatriol, which was degraded from Panax quinquefolium saponin with sodium in glycerine, extracted and seperated by flash chromatography. Three six-membered rings are in chair conformations, the five-membered ring is in an envelope form and the tetrahydrofuran ring has a conformation intermediate between half-chair and envelope. In the crystal, molecules are linked by O—H⋯O hydrogen bonds, and C—H⋯O contacts also occur. The absolute structure was assigned on the basis of the synthesis.

(3S,12R,20S,24R)-20,24-Ep-oxy-dammarane-3,12,25-triol.

In the title molecule, C30H52O4, the three six-membered rings are in chair conformations, the cyclopentane ring is in an envelope form and the tetrahydrofuran ring has a conformation intermediate between half-chair and sofa. In the crystal, molecules are linked by intermolecular O—H⋯O hydrogen bonds into helical chains along [100]. Two intramolecular O—H⋯O hydrogen bonds are also present. One C atom of the tetrahydrofuran ring and its attached H atoms are equally disordered over two sets of sites.

N-Cyclo-propyl-N-[2-(2,4-difluoro-phen-yl)-2-hy-droxy-1-(1H-1,2,4-triazol-1-yl)prop-yl]-2-(5-methyl-2,4-dioxo-1,2,3,4-tetra-hydro-pyrimidin-1-yl)acetamide dichloro-methane 0.62-solvate.

In the title compound, C21H22F2N6O4·0.62CH2Cl2, the difluoro-substituted benzene ring forms dihedral angles of 54.6 (3)° with the mean plane of the thymine ring and 50.9 (2)° with the triazole ring. The dihedral angle between the thymine and triazole rings is 7.4 (3)°. In the crystal, intermolecular N—H⋯N and O—H⋯O hydrogen bonds link the main molecules into chains along [10]. The CH2Cl2 solvent molecule was refined as partial occupancy over two sets of sites with refined occupancies of 0.308 (9) and 0.310 (8).