COPPER ACYL SALICYLATE HAS POTENTIAL AS AN ANTI-CRYPTOCOCCUS ANTI-FUNGAL AGENT [PublishAheadOfPrint]

The in vitro anti-fungal activity of aspirin against cryptococcal cells has been reported. However, its undesired effects may limit its clinical application. Conceivably, a derivative of aspirin could overcome this challenge. Toward this end, this paper considered the usage of an aspirinate-metal complex viz. copper acyl salicylate (CAS) as an anti-Cryptococcus anti-fungal agent. Additionally, the paper examined the influence of this compound on macrophage function. The in vitro susceptibility results revealed that cryptococcal cells were vulnerable (in a dose-dependent manner) to CAS, which may have effected growth inhibition by damaging cryptococcal cell membranes. Interestingly, when used in combined therapy with fluconazole or amphotericin B, synergism was observed. Furthermore, CAS did not negatively affect the growth as well as the metabolic activity of macrophages rather it sensitised these immune cells to produce INF-y and IL-6, which, in turn, may have aided in the phagocytosis of cryptococcal cells. When compared to our aspirin data, CAS was noted to be more effective in killing cryptococcal cells (based on susceptibility results) and less toxic towards macrophages (based on growth inhibition results). Taken together, it is reasonable to conclude that CAS may be a better anti-Cryptococcus drug that could deliver better therapeutic outcomes when compared to aspirin.

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