Caspofungin - CAS 162808-62-0

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CAS 162808-62-0 Caspofungin
Reference Reading
1. Surface coatings with covalently attached caspofungin are effective in eliminating fungal pathogens
Bryan R. Coad,* Stephanie J. Lamont-Friedrich. J. Mater. Chem. B, 2015, 3, 8469—8476
Echinocandins were incubated with aldehyde-bearing surfaces and reductive amination was carried out using sodium cyanoborohydride. Then surfaces were washed using PBS solution alone, PBS followed by SDS solution, or PBS followed by SDS solution at 70 ℃. XPS revealed the relative amount of nitrogen remaining on the surface after washing (Fig. 3). The presence of nitrogen in the PBS-washed samples showed that all three echinocandins have the ability to adsorb to aldehyde plasma polymer surfaces. Using SDS washing, anidulafungin could be completely desorbed and small amounts of reversibly-adsorbed micafungin and caspofungin could be removed. These reductions are likely explained by the disruption of weak physical forces holding them to the surface. When washed with SDS at 70 ℃, physisorbed micafungin could be completely removed along with an additional loss of 0.4% N for caspofungin. The fact that only caspofungin (which amongst these echinocandins is capable of forming amine bonds with aldehyde-functionalized surfaces) remains after aggressive washing suggests that SDS washing at 70 ℃ is required to remove physisorbed compounds.
2. Review on fungal enzyme inhibitors–potential drug targets to manage human fungal infections
Jayapradha Ramakrishnan, Sudarshan Singh Rathore and Thiagarajan Raman*. RSC Adv.,2016, 6,42387–42401
Adaptive stress response is another potential echinocandin resistancemechanism. The highly dynamic nature of the fungal cell wall allows it to synthesize cell wall components even if any specific cell wall biosynthetic pathway is inhibited. Echinocandins induce a set of genes including HOG1, CEK1 and PKC MAP kinase cascade which is involved in the alteration of protein kinase C/Ca2+/calcineurin/Crz1, and high osmolarity glycerol, which results in compensatory increases in chitin synthesis. An increase in chitin synthesis protects against destabilizing environmental stresses created by echinocandin exposure. However, echinocandin resistance is uncommon unless other conditions like repeated therapy are undertaken among immunosuppressed patients. Moreover, echinocandins and chitin synthase inhibitors like calcineurin inhibitors, FK506 and cyclosporin A have been shown to demonstrate synergism, highlighting the potential for combination therapies with enhanced antifungal activity against A. fumigatus and C. neoformans. In addition, few in vitro studies have observed the supra MIC concentration of caspofungin in C. albicans strains. This is known as the paradoxical effect, wherein it synthesizes more chitin at low concentrations of caspofungin. The details of the therapeutic applications of antifungal agents are discussed in Table 2.
3. A sensitive liquid chromatography-tandem mass spectrometry method for monitoring the caspofungin trough plasma concentration and its association with caspofungin efficacy in intensive-care-unit patients
Qianting Yang, Taotao Wang, Yalin Dong. RSC Adv.,2015, 5,104806–104814
Invasive fungal infections (IFIs) have high morbidity and mortality, and are the fourth most common cause of nosocomial infections in intensive care unit (ICU) patients, accounting for about one in five of all infections in critically ill patients. ICU patients are susceptible to fungal infections because they often suffer from multiple diseases and organ dysfunction after receiving major surgery that involves postoperative catheter indwelling. Caspofungin was the first antifungal agent of the echinocandin family approved for the treatment of IFIs caused by Candida spp. and Aspergillus spp. in patients who are refractory to or intolerant of voriconazole.Caspofungin works by inhibiting the synthesis of β-(1,3)-D-glucan, which is an essential component of Candida and Aspergillus cell walls. The recommended dosage regimen of caspofungin is a loading dose of 70 mg followed by 50 mg daily that is administered intravenously over a 1 h period. Caspofungin is highly protein-bound (~96%) and metabolizes slowly in the liver. It is eliminated slowly from plasma, with a clearance rate of 10–12 mL min -1 and a half-life of 9–11 h.
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