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.
Highlights
Aspergillus fumigatus is an opportunistic filamentous mould responsible for more than 90% of infections caused due to Aspergillus [1]
In an effort to explore potent anti-Aspergillus molecules, present study was aimed to examine the safety and antifungal efficacy of SCD-1, a synthetic coumarin derivative using mouse model
Coumarins have been explored for their biological properties such as anti-inflammatory, cytotoxic, anti-tubercular and angiogenic [19,20,21,22] etc, studies focusing on their antifungal efficacy are limited in number, only in vitro antifungal activity has been indicated in some reports [29,30]
Summary
Aspergillus fumigatus is an opportunistic filamentous mould responsible for more than 90% of infections caused due to Aspergillus [1]. The lipid formulations of Amphotericin B have been developed to overcome its dose-dependent toxicity but less toxic, they are expensive [10] and exhibit variability in their pharmacokinetics, tissue distribution and safety levels [11,12]. Another class of antifungal agents is azoles, among them, voriconazole has been used for the primary therapy for IA, with posaconazole and itraconazole as the drugs for salvage therapy [13]. The echinocandins have been most promising but are available only as parenteral formulations [16]
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