8 research outputs found

    Cellular apoptosis and cell cycle arrest as potential therapeutic targets for eugenol derivatives in Candida auris

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    Candida auris, the youngest Candida species, is known to cause candidiasis and candidemia in humans and has been related to several hospital outbreaks. Moreover, Candida auris infections are largely resistant to the antifungal drugs currently in clinical use, necessitating the development of novel medications and approaches to treat such infections. Following up on our previous studies that demonstrated eugenol tosylate congeners (ETCs) to have antifungal activity, several ETCs (C1-C6) were synthesized to find a lead molecule with the requisite antifungal activity against C. auris. Preliminary tests, including broth microdilution and the MUSE cell viability assay, identified C5 as the most active derivative, with a MIC value of 0.98 g/mL against all strains tested. Cell count and viability assays further validated the fungicidal activity of C5. Apoptotic indicators, such as phosphatidylserine externalization, DNA fragmentation, mitochondrial depolarization, decreased cytochrome c and oxidase activity and cell death confirmed that C5 caused apoptosis in C. auris isolates. The low cytotoxicity of C5 further confirmed the safety of using this derivative in future studies. To support the conclusions drawn in this investigation, additional in vivo experiments demonstrating the antifungal activity of this lead compound in animal models will be needed

    Hemolytic activity of C-5.

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    Hemolysis of horse red blood cells was done in presence of Triton-X (control) and different concentrations of C-5.</p

    Minimum inhibitory concentrations (MIC) and minimum fungicidal concentrations (MFC) of eugenol tosylate congeners (C1-C6) against different <i>C</i>. <i>auris</i> isolates.

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    Minimum inhibitory concentrations (MIC) and minimum fungicidal concentrations (MFC) of eugenol tosylate congeners (C1-C6) against different C. auris isolates.</p

    Probing the antibacterial and anticancer potential of tryptamine based mixed ligand Schiff base Ruthenium(III) complexes

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    Development of new chemotherapeutic agents to treat microbial infections and recurrent cancers is of pivotal importance. Metal based drugs particularly ruthenium complexes have the uniqueness and desired properties that make them suitable candidates for the search of potential chemotherapeutic agents. In this study, two mixed ligand Ru(III) complexes Ru(Cl)(2)(SB)(Phen] (RC-1) and Ru(Cl)(2)(SB)(Bipy)] (RC-2) were synthesised and characterized by elemental analysis, IR, UV-Vis, H-1, C-13 NMR spectroscopic techniques and their molecular structure was confirmed by X-ray crystallography. Antibacterial activity evaluation against two Gram-positive (S. pneumonia and E. faecalis) and four Gram-negative strains (P. aurogenosa, K. pneumoniae, S. enterica, and E. coli) revealed their moderate antibacterial activity with MIC value of >= 250 mu g/mL. Anticancer activity evaluation against a non-small lung cancer cell line (H1299) revealed the tremendous anticancer activity of these complexes which was further validated by DNA binding and docking results. DNA binding profile of the complexes studied by UV-Visible and fluorescence spectroscopy showed an intercalative binding mode with CT-DNA and an intrinsic binding constant in the range of 3.481-1.015 x 10(5) M-1. Both the complexes were also found to exert weak toxicity to human erythrocytes by haemolytic assay compared to cisplatin. Potential of these complexes as anticancer agents will be further delineated by in vivo studies

    TUNNEL assay representing apoptosis in <i>C</i>. <i>auris</i>.

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    The confocal microscopy of C. auris 6057 cells treated with different concentrations (½MIC, MIC, and 2MIC) of C-5 compound. Hoechst 33342 dye (blue fluorescence) showing live cells, and Alexa Fluor 488 dye (green fluorescence) represent apoptotic cells.</p
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