Browsing by Author "Ghosh, Chandradhish"

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    Aryl-alkyl-lysines: Novel agents for treatment of C. difficile infection
    Ghosh, Chandradhish; AbdelKhalek, Ahmed; Mohammad, Haroon; Seleem, Mohamed N.; Haldar, Jayanta (Nature Publishing Group, 2020-03-27)
    Clostridium difficile infections (CDIs) are a growing health concern worldwide. The recalcitrance of C. difficile spores to currently available treatments and concomitant virulence of vegetative cells has made it imperative to develop newer modalities of treatment. Aryl-alkyl-lysines have been earlier reported to possess antimicrobial activity against pathogenic bacteria, fungi, and parasites. Their broad spectrum of activity is attributed to their ability to infiltrate microbial membranes. Herein, we report the activity of aryl-alkyl-lysines against C. difficile and associated pathogens. The most active compound NCK-10 displayed activity comparable to the clinically-used antibiotic vancomycin. Indeed, against certain C. difficile strains, NCK-10 was more active than vancomycin in vitro. Additionally, NCK-10 exhibited limited permeation across the intestinal tract as assessed via a Caco-2 bidirectional permeability assay. Overall, the findings suggest aryl-alkyl-lysines warrant further investigation as novel agents to treat CDI.
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    Non-Toxic Glycosylated Gold Nanoparticle-Amphotericin B Conjugates Reduce Biofilms and Intracellular Burden of Fungi and Parasites
    Ghosh, Chandradhish; Varela-Aramburu, Silvia; Eldesouky, Hassan E.; Salehi Hossainy, Sharareh; Seleem, Mohamed N.; Aebischer, Toni; Seeberger, Peter H. (2021-03-18)
    Infections by intracellular pathogens cause significant morbidity and mortality due to lack of efficient drug delivery. Amphotericin B, currently used to treat leish maniasis and cryptococcosis, is very toxic and cannot eradicate intracellular Cryptococcus neoformans (C. neoformans). Glycosylated gold nanoparticles are water dispersible and biocompatible with very little toxici ty. While amphotericin B is insoluble in water at neutral pH, conjugates of amphotericin B and ultra-small gold nanoparticles (AuNP) are better dispersible in water. Amphotericin B conjugated glycosylated gold nanoparticles (AmpoB@AuNP) are more efficacious in treating both extracellular and intracellular forms of Leishmania mexicana (L. mexicana) than amphotericin B alone. In addition, AmpoB@AuNP are effective in reducing C. neoformans biofilms by 80% and intracellular C. neoformans burden by >90%. Furthermore, AmpoB@AuNP are not haemolytic at 50 mu g mL(-1) and are significantly less toxic to murine macrophages than amphotericin B. Ultra-small AuNPs are attractive delivery agents to treat intracellular infections and AmpoB@AuNP may be useful for treating C. neoformans infections in immunocompromised patients.