Cell lines

Aspergillus fumigates

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

32 μg/ml for 6 h; or 2 μg/ml for 12 h

Applications

Caspofungin suppressed the synthesis of cell wall β-1,3-glucan, which triggered a compensatory stimulation of chitin synthesis. Caspofungin induced morphological changes in Aspergillus fumigates. Moreover, Treatment with caspofungin induced ChsG-dependent upregulation of chitin synthesis and the formation of chitin-rich microcolonies in Aspergillus fumigates.

Caspofungin acetate(MK-0991), a new antifungal agent with minimal toxicity, inhibits synthesis of 1,3-β-D-glucan, an essential component of the fungal cell wall [1].

In vitro: Incubation ofA. fumigatuwith a single dose of caspofungin affected the same proportion of apical and subapical branching cells for up to 72 h.The cells at the active centers for new cell wall synthesis withinA. fumigateshyphae are killed when they are exposed to caspofungin [1]. Caspofungin acetate irreversibly inhibited the enzyme 1,3-β-D-glucan synthase, preventing the formation of glucan polymers and disrupting the integrity of the fungal cell wall. The elimination half-life of caspofungin acetate was 9-10 hours [2]. Caspofungin showed activity againstAspergillusspp. as well as a variety ofCandidaspp[3]. Growth kinetic studies of caspofungin acetate against Candida albicans and Candida tropicalis isolates showed that caspofungin acetate exhibited fungicidal activity (i.e., a 99% reduction in viability) within 3 to 7 h at concentrations ranging from 0.06 to 1 μg/ml (0.25 to 4 times the MIC)[4].The minimal inhibitory concentration for 90% inhibition of Candida species by caspofungin acetate were as follows:C. albicans 0.5 μg/mL (range, 0.25-0.5), C. glabrata 1.0 μg/mL (range, 0.25-2.0), C. tropicalis 1.0 μg/mL (range, 0.25-1.0), C. parapsilosis 0.5 μg/mL (range, 0.25-1.0), and C. krusei 2.0 μg/mL (range, 0.5-2.0)[4].

Clinical trials: In a trial of 128 patients with Candida esophagitis, clinical response rates were higher with caspofungin acetate 50 or 70 mg/day (85%) than with amphotericin B 0.5 mg/kg/day (67%)[2].

References:
[1]. Bowman J C, Hicks P S, Kurtz M B, et al. The antifungal echinocandincaspofungin acetate kills growing cells of Aspergillus fumigatus in vitro[J]. Antimicrobial agents and chemotherapy, 2002, 46(9): 3001-3012.
[2]. Hoang A. Caspofungin acetate: an antifungal agent[J]. American journal of health-system pharmacy, 2001, 58(13): 1206-1214.
[3]. Pacetti S A, Gelone S P. Caspofungin acetate for treatment of invasive fungal infections[J]. Annals of Pharmacotherapy, 2003, 37(1): 90-98.
[4]. Bartizal K, Gill C J, Abruzzo G K, et al. In vitro preclinical evaluation studies with the echinocandin antifungal MK-0991 (L-743,872)[J]. Antimicrobial Agents and Chemotherapy, 1997, 41(11): 2326-2332.