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In Vitro and In Vivo Evaluation of Small Cationic Abiotic Lipopeptides as Novel Antifungal Agents
Author(s) -
Lohan Sandeep,
Monga Jitender,
Chauhan Chetan Singh,
Bisht Gopal Singh
Publication year - 2015
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12558
Subject(s) - aspergillus fumigatus , calcein , in vivo , in vitro , antifungal , potency , microbiology and biotechnology , minimum inhibitory concentration , biology , cytotoxicity , antimicrobial , membrane , chemistry , biochemistry
We investigated the antifungal potential of short lipopeptides against clinical fungal isolates with an objective to evaluate their clinical feasibility. All tested lipopeptides exhibit good antifungal activity with negligible difference between the MIC s against susceptible and drug‐resistant clinical fungal isolates. The MTT assay results revealed the lower cytotoxicity of lipopeptides toward mammalian cells ( NRK ‐52E). In particular, LP 24 displayed highest potency against most of the tested fungal isolates with MIC s in the range of 1.5–4.5  μ g/mL. Calcein dye leakage experiments with model membrane suggested the membrane‐active mode of action for LP 24. Extending our work from model membranes to intact Aspergillus fumigatus in scanning electron micrographs, we could visualize surface perturbation caused by LP 24. LP 24 (5 mg/kg) significantly reduces the A. fumigatus burden among the various organs of infected animals, and 70% of the infected mice survived when observed for 28 days. This study underscores the potential of small cationic abiotic lipopeptides to develop into the next‐generation antimicrobial therapy.

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