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Chemical Structure| 179463-17-3 Chemical Structure| 179463-17-3

Structure of Caspofungin diacetate
CAS No.: 179463-17-3

Chemical Structure| 179463-17-3

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Caspofungin acetate is an lipopeptide antifungal β-1,3-glucan synthase inhibitor.

Synonyms: MK-0991 diacetate; L-743872 diacetate; MK 0991

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Product Citations

Product Citations

Tancer, Robert J ; Pawar, Siddhi ; Wang, Yina ; Ventura, Cristina R ; Wiedman, Gregory ; Xue, Chaoyang

Abstract: Fungal infections in humans are difficult to treat, with very limited drug options. Due to a confluence of factors, there is an urgent need for innovation in the drug space, particularly to combat increasing antifungal drug resistance. Our previous studies showed that Cdc50, a subunit of fungal lipid translocase (flippase), is essential for Cryptococcus neoformans virulence and required for drug resistance, suggesting that fungal lipid flippase could be a novel drug target. Here, we characterized an antifungal peptide, Cryptomycinamide (KKOO-NH2), derived from a 9-amino acid segment of the C. neoformans Cdc50 protein. A fungal killing assay indicated that KKOO-NH2 is fungicidal against C. neoformans. The peptide has activity against multiple major fungal pathogens with a minimum inhibitory concentration (MIC) of 8 μg/mL against C. neoformans and Candida glabrata, 16 μg/mL against Candida albicans and C. auris, and 32 μg/mL against Aspergillus fumigatus. The peptide has low cytotoxicity against host cells based on our hemolysis assays and vesicle leakage assays. Strikingly, the peptide exhibits strong drug synergy with multiple drugs, including , itraconazole, and caspofungin, depending on the specific species on which the combinations were assayed. The fluorescently labeled peptide was detected to localize to the plasma membrane, likely inhibiting key interactions of Cdc50 with membrane proteins such as P4 ATPases. Cryptococcus cells exposed to sub-MIC of peptide showed increased reactive oxygen species production and intracellular calcium levels, indicating a peptide-induced stress response. Decreased intracellular proliferation within macrophages was observed after 30 min of peptide exposure and 24 h coincubation with macrophages, providing a potential translational mechanism to explore further in vivo. In aggregate, the synergistic activity of our KKOO-NH2 peptide may offer a potential novel candidate for combination therapy with existing drugs.

Keywords: antifungal peptide ; drug resistance ; pathogenic fungi ; cdc50 ; lipid flippase

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Product Details of Caspofungin diacetate

CAS No. :179463-17-3
Formula : C56H96N10O19
M.W : 1213.42
SMILES Code : CC(O)=O.O=C1N2[C@]([C@H](CC2)O)([H])C(N[C@@H]([C@@H](C[C@@H](C(N[C@@](C(N3[C@](C[C@H](C3)O)([H])C(N[C@@](C(N[C@@]1([H])[C@H](O)CCN)=O)([H])[C@H](O)[C@H](C4=CC=C(C=C4)O)O)=O)=O)([H])[C@H](O)C)=O)NC(CCCCCCCC[C@@H](C)C[C@@H](C)CC)=O)O)NCCN)=O.CC(O)=O
Synonyms :
MK-0991 diacetate; L-743872 diacetate; MK 0991
MDL No. :MFCD08141839

Safety of Caspofungin diacetate

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Candida albicans SC5314 0.125 μg/ml 12 h To evaluate the antifungal effect of MG combined with CAS on C. albicans SC5314, the results showed that the combination significantly enhanced the antifungal effect. PMC7801120
Candida albicans CAS-resistant strain S20 0.25 μg/ml 12 h To evaluate the antifungal effect of MG combined with CAS on CAS-resistant strain S20, the results showed that the combination significantly enhanced the antifungal effect. PMC7801120
Candida albicans yeast cells 46.9 ng/mL 30 minutes To study the effect of Caspofungin on β(1,3)-glucan exposure and chitin synthesis, results showed that Caspofungin treatment significantly increased chitin levels and β(1,3)-glucan unmasking. PMC10470516
Candida albicans hyphal cells 46.9 ng/mL 30 minutes To study the effect of Caspofungin on β(1,3)-glucan exposure in hyphal cells, results showed that Caspofungin treatment increased β(1,3)-glucan exposure on the hyphal cell wall. PMC10470516
Aspergillus fumigatus conidia 8 mg/mL 5 days To evaluate the growth effect of caspofungin on Aspergillus fumigatus conidia, results showed that all conidia could grow in high concentrations of caspofungin PMC9239232
Candida glabrata 0.032-8 μg/ml 6 hours Candida glabrata and Candida guilliermondii, which had naturally more β-1,3-glucan exposed on the cell surface, were phagocytosed significantly more efficiently by J774 macrophages. PMC7247809
Aspergillus fumigatus 16 μg/ml To assess the role of transcription factors in the caspofungin paradoxical effect, 11 TF mutants were identified that showed reduced sensitivity at 16 μg/ml caspofungin. PMC7298710

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
BALB/c mice Disseminated candidiasis model Intraperitoneal injection 0.03 mg/kg Days 0, 1, 2, 4, and 6 To evaluate the therapeutic effect of MG combined with CAS on disseminated candidiasis, the results showed that the combination significantly improved the survival rate of mice. PMC7801120

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

0.82mL

0.16mL

0.08mL

4.12mL

0.82mL

0.41mL

8.24mL

1.65mL

0.82mL

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