title: In Vitro and In Vivo Evaluation of Small Cationic Abiotic Lipopeptides as Novel Antifungal Agents.
abstract: 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 MICs 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, LP24 displayed highest potency against most of the tested fungal isolates with MICs in the range of 1.5-4.5 μg/mL. Calcein dye leakage experiments with model membrane suggested the membrane-active mode of action for LP24. Extending our work from model membranes to intact Aspergillus fumigatus in scanning electron micrographs, we could visualize surface perturbation caused by LP24. LP24 (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.
authors.affiliation: Department of Pharmacy, Jaypee University of Information Technology, Solan, 173234, India.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Lohan
authors.affiliation: Department of Urology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
authors.forename: Jitender
authors.initials: J
authors.lastname: Monga
authors.affiliation: Department of Pharmacy, Bhupal Noble College of Pharmacy, Udaipur, Rajasthan, 313002, India.
authors.forename: Chetan Singh
authors.initials: CS
authors.lastname: Chauhan
authors.affiliation: Department of Pharmacy, Jaypee University of Information Technology, Solan, 173234, India.|Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Solan, 173234, India.
authors.forename: Gopal Singh
authors.initials: GS
authors.lastname: Bisht
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy*; D001232:Aspergillus fumigatus / Q000187:drug effects*; D001234:Aspergillus niger / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy; D002460:Cell Line; D003453:Cryptococcosis / Q000188:drug therapy; D003455:Cryptococcus neoformans / Q000187:drug effects; D006801:Humans; D055666:Lipopeptides / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008826:Microbial Sensitivity Tests
chemical_list: D000935:Antifungal Agents; D055666:Lipopeptides
keywords: antibiotic resistance; antifungal activity; cytotoxicity; lipopeptide; membrane active