Identification of novel antifungal agents: antimicrobial evaluation, SAR, ADME-Tox and molecular docking studies of a series of imidazole derivatives.

Thirty-four imidazole-based compounds synthesized by one-pot catalytic method were evaluated for their antifungal and antibacterial activities against several fungal and bacterial strains. None of the compounds had antibacterial activity. Interestingly, compounds 1, 2, 3, 10 and 15 displayed a strong antifungal activity against all the tested fungal species, while compounds 5, 7, 9, 11, 21 and 27 showed a moderate antifungal activity. To better understand the biological activity of the most active compounds ADME-Tox and molecular docking studies were carried out. Interestingly, compounds 1, 2, 3, 7, 10 and 15 showed excellent bioavailability. In addition, compounds 1, 2 and 3, exhibited good toxicity profiles. Docking studies of the two most active compounds 2 (IC50 of 95 ± 7.07 µM) and 10 (IC50 of 235 ± 7.07 µM) suggested that they might act by inhibiting the fungal lanosterol 14α-demethylase. Therefore, these novel antifungal agents merit further characterization for the development of new antifungal therapeutics.

In vitro screening, homology modeling and molecular docking studies of some pyrazole and imidazole derivatives.

A series of synthesized compounds based on pyrazole and imidazole skeletons prepared by palladium catalysts via a one-pot reaction was screened to determine their inhibitory potency against the pathogen fungus Fusarium oxysporum f.sp. albedinis (F.o.a) and four bacteria strains namely Micrococcus luteus, Bacillus subtilis, Staphylococcus aureus and Escherichia coli. The obtained result showed that these compounds exhibit an efficiency antifungal action. Whereas, they showed a very weak antibacterial activity. The structure-activity relationship (SAR) Analysis and lipophilicity study demonstrates the presence of a strong relation between the structure of the ligands and the antifungal activity. On the other hand, a homology modeling and molecular docking study was carried out on the most active compounds against F.o.a fungus, in order to understand and determine the molecular interactions taking place between the ligand and the corresponding receptor of the studied target.

New N,N,N',N'-tetradentate Pyrazoly Agents: Synthesis and Evaluation of their Antifungal and Antibacterial Activities.

A new library of N,N,N',N' -tetradentate pyrazoly compounds containing a pyrazole moiety was synthesized by the condensation of (3,5-dimethyl-1H-pyrazol-1-yl)methanol 2a or (1H-pyrazol-1-yl)methanol 2b with a series of primary diamines in refluxed acetonitrile for 6h. The antifungal activity against the budding yeast Saccharomyces cerevisiae, as well as the antibacterial activity against Escherichia coli of these new tetradentate ligands were studied. We found that these tetradentate ligands act specifically as antifungal agents and lack antibacterial activity. Their biological activities depend on the nature of the structure of the compounds.