Efficacy of Novel Schiff base Derivatives as Antifungal Compounds in Combination with Approved Drugs Against Candida Albicans.

BACKGROUND: The increasing incidence of fungal infections, especially caused by Candida albicans, and their increasing drug resistance has drastically increased in recent years. Therefore, not only new drugs but also alternative treatment strategies are promptly required. METHODS: We previously reported on the synergistic interaction of some azole and non-azole compounds with fluconazole for combination antifungal therapy. In this study, we synthesized some non-azole Schiff-base derivatives and evaluated their antifungal activity profile alone and in combination with the most commonly used antifungal drugs- fluconazole (FLC) and amphotericin B (AmB) against four drug susceptible, three FLC resistant and three AmB resistant clinically isolated Candida albicans strains. To further analyze the mechanism of antifungal action of these compounds, we quantified total sterol contents in FLC-susceptible and resistant C. albicans isolates. RESULTS: A pyrimidine ring-containing derivative SB5 showed the most potent antifungal activity against all the tested strains. After combining these compounds with FLC and AmB, 76% combinations were either synergistic or additive while as the rest of the combinations were indifferent. Interestingly, none of the combinations was antagonistic, either with FLC or AmB. Results interpreted from fractional inhibitory concentration index (FICI) and isobolograms revealed 4-10-fold reduction in MIC values for synergistic combinations. These compounds also inhibit ergosterol biosynthesis in a concentration-dependent manner, supported by the results from docking studies. CONCLUSION: The results of the studies conducted advocate the potential of these compounds as new antifungal drugs. However, further studies are required to understand the other mechanisms and in vivo efficacy and toxicity of these compounds.

Heterocyclic Schiff base transition metal complexes in antimicrobial and anticancer chemotherapy.

In recent years, the number of people suffering from cancer and multidrug-resistant infections has sharply increased, leaving humanity without any choice but to search for new treatment options and strategies. Although cancer is considered the leading cause of death worldwide, it also paves the way many microbial infections and thus increases this burden manifold. Development of small molecules as anticancer and anti-microbial agents has great potential and a plethora of drugs are already available to combat these diseases. However, the wide occurrence of multidrug resistance in both cancer and microbial infections necessitates the development of new and potential molecules with desired properties that could circumvent the multidrug resistance problem. A successful strategy in anticancer chemotherapy has been the use of metallo-drugs and this strategy has the potential to be used for treating multidrug-resistant infections more efficiently. As a class of molecules, Schiff bases have been the topic of considerable interest, owing to their versatile metal chelating properties, inherent biological activities and flexibility to modify the structure to fine-tune it for a particular biological application. Schiff base-based metallo-drugs are being researched to develop new anticancer and anti-microbial chemotherapies and because both anticancer and anti-microbial targets are different, heterocyclic Schiff bases can be structurally modified to achieve the desired molecule, targeting a particular disease. In this review, we collect the most recent and relevant literature concerning the synthesis of heterocyclic Schiff base metal complexes as anticancer and anti-microbial agents and discuss the potential and future of this class of metallo-drugs as either anticancer or anti-microbial agents.

Synthesis of Ni(II), Cu(II) and Co(II) complexes with new macrocyclic Schiff-base ligand containing dihydrazide moiety: Spectroscopic, structural, antimicrobial and antioxidant properties.

In this study, the macrocyclic Schiff base ligand (L) derived from 1, 4-dicarbonyl-phenyl-dihydrazide and glyoxal (2:2) and its Ni (II), Cu (II) and Co(II) complexes were synthesised and were characterised by elemental analyses, FTIR, UV-Vis., mass and 1H NMR. The ligand (L) behaves as a tetradentate ligand and coordinates to the metal ions via the nitrogen atoms and the complexes have the mononuclear structures. The synthesised compounds were evaluated for their inhibition potential against bacterial and fungal strains and the assay indicated that the metal complexes exhibited a remarkable antibacterial and antifungal activity against these tested strains. In addition, the antioxidant activity of the compounds was also studied through scavenging effect on DPPH radicals with the copper complex showing enhanced antioxidant activity than other metal complexes.

Design, synthesis and spectroscopic characterization of metal (II) complexes derived from a tetradentate macrocyclic ligand: Study on antimicrobial and antioxidant capacity of complexes.

The paper presents the synthesis of Co(II), Ni(II) and Cu(II) complexes of macrocyclic Schiff base ligand derived from 1, 4-dicarbonyl-phenyl-dihydrazide and ethyl 3-oxobutanoate (2:2). The synthesized ligand and its metal complexes were characterized by elemental analyses, magnetic susceptibility measurements, FTIR, UV-Vis., mass 1H NMR and X-ray diffraction. The Cu(II) complex exhibit distorted octahedral geometry, whereas an octahedral geometry is suggested for other complexes. The synthesized compounds were screened in vitro for their antimicrobial activities to evaluate their inhibiting potential against bacterial species Pseudomonas aeruginosa, Escherichia coli, Salmonella typhimurium, Staphylococcus aureus and fungal species include Aspergillus flavus, Aspergillus fumingatus, and Candida albicans. The complexation led to a remarkable increase in antimicrobial activity. In addition, the antioxidant activity of the compounds was also investigated through scavenging effect on DPPH radicals. The obtained IC50 value of the DPPH activity for the copper complex was higher than other compounds.

Design, synthesis, characterization and antimicrobial/antioxidant activities of 1, 4-dicarbonyl-phenyl-dihydrazide based macrocyclic ligand and its Cu(II), Co(II) and Ni(II) complexes.

Mononuclear transition metal complexes of Cu(II), Co(II) and Ni(II) with a newly synthesised macrocyclic ligand derived from 1, 4-dicarbonyl-phenyl-dihydrazide and 1,2-diphenylethane-1,2-dione (2:2) have been synthesised. The synthesised compounds were characterised by various physical and spectroscopic techniques including elemental analysis, FTIR, Uv-Vis., 1H NMR, mass spectra, magnetic moment and XRD. The investigation of these macrocyclic complexes established that the stability of metal-ligand coordination through N atoms as tetradentate chelates. The metal/ligands ratio of 1:1 was proposed to afford octahedral geometry for the complexes. The antimicrobial activity of the compounds against some bacterial and fungal species were done by well diffusion method and the results shows that the metal complexes have a promising biological activity comparable with the parent ligand against all bacterial and fungal species. The antioxidant activity of the compounds was also studied through scavenging effect on DPPH radicals with the copper complex showing enhanced activity than other compounds. Additionally, the docking studies predicted the high antimicrobial activity due to the interaction of ligand with the protein.