title: In vivo efficacy of a synthetic coumarin derivative in a murine model of aspergillosis.
abstract: Despite advances in therapeutic modalities, aspergillosis remains a leading cause of mortality. This has necessitated the identification of effective and safe antifungal molecules. In the present study, in vivo safety and antifungal efficacy of a coumarin derivative, N, N, N-Triethyl-11-(4-methyl-2-oxo-2H-benzopyran-7-yloxy)-11-oxoundecan-1-aminium bromide (SCD-1), was investigated. The maximum tolerable dose of compound was determined according to OECD 423 guidelines. The compound could be assigned to category IV of the Globally Harmonized System and its LD50 cut-off was found to be 2000 mg/kg body weight. The survival increased in Aspergillus fumigatus-infected mice treated with a dose of 200 mg/kg, orally or 100 mg/kg body weight, intraperitoneally, of SCD-1 in comparison to infected-untreated animals. The SCD-1 treatment resulted in significant reduction in colony counts in vital organs of the animals. Its protective effect was also observed on day 14 as there was marked reduction in fungal colonies. The treatment with SCD-1 also reduced the levels of serum biochemical parameters with respect to infected-untreated animals. It could be concluded that SCD-1 is a quite safe antifungal compound, which conferred dose dependent protection against experimental aspergillosis. Therefore, SCD-1 holds potential for developing new formulations for aspergillosis.
authors.affiliation: Diagnostic Biochemistry, CSIR-Institute of Genomics and Integrative Biology, Delhi, India; Department of Biotechnology, University of Pune, Pune, India.
authors.forename: Seema
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Biochemistry, Maharishi Dayanand University, Rohtak, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Dabur
authors.affiliation: Department of Pharmacology and Toxicology, Bombay Veterinary College, Parel, Mumbai, India.
authors.forename: Madhumanjiri M
authors.initials: MM
authors.lastname: Gatne
authors.affiliation: Diagnostic Biochemistry, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Bharat
authors.initials: B
authors.lastname: Singh
authors.affiliation: Department of Chemistry, University of Delhi, New Delhi, India.
authors.forename: Shilpi
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Pharmacology, National Research Institute of Basic Ayurvedic Sciences, Kothrud, Pune, India.
authors.forename: Sharad
authors.initials: S
authors.lastname: Pawar
authors.affiliation: Department of Chemistry, University of Delhi, New Delhi, India.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Sharma
authors.affiliation: Diagnostic Biochemistry, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Gainda L
authors.initials: GL
authors.lastname: Sharma
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy*; D001232:Aspergillus fumigatus / Q000254:growth & development; D015169:Colony Count, Microbial; D003374:Coumarins / Q000627:therapeutic use*; D004195:Disease Models, Animal; D051379:Mice; D000644:Quaternary Ammonium Compounds / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D003374:Coumarins; C000593034:N,N,N-triethyl-11-(4-methyl-2-oxo-2H-chromen-7-yloxy)-11-oxoundecan-1-aminium; D000644:Quaternary Ammonium Compounds