Department of Microbial, Biochemical, and Food Biotechnology, University of the Free State, Bloemfontein, South Africa.
Department of Health Sciences, Central University of Technology, Bloemfontein, South Africa.
Antimicrob Agents Chemother. 2018 Jul 27;62(8). doi: 10.1128/AAC.02345-17. Print 2018 Aug.
The antifungal activity of aspirin against cryptococcal cells has been reported. However, the unwanted effects of aspirin may limit its clinical application. Conceivably, a derivative of aspirin could overcome this challenge. Toward this end, this study considered the usage of an aspirinate-metal complex, namely, copper acyl salicylate (CAS), as an anti- antifungal agent. Additionally, the study examined the effects of this compound on macrophage function. The susceptibility results revealed that cryptococcal cells were vulnerable (in a dose-dependent manner) to CAS, which might have effected growth inhibition by damaging cryptococcal cell membranes. Interestingly, when CAS was used in combination with fluconazole or amphotericin B, synergism was observed. Furthermore, CAS did not negatively affect the growth or metabolic activity of macrophages; rather, it sensitized those immune cells to produce interferon gamma and interleukin 6, which, in turn, might have aided in the phagocytosis of cryptococcal cells. Compared to our aspirin data, CAS was noted to be more effective in killing cryptococcal cells (based on susceptibility results) and less toxic toward macrophages (based on growth inhibition results). Taking these findings together, it is reasonable to conclude that CAS may be a better anti- drug that could deliver better therapeutic outcomes, compared to aspirin.
阿司匹林对隐球菌细胞的抗真菌活性已有报道。然而，阿司匹林的不良反应可能会限制其临床应用。可以想象，阿司匹林的衍生物可以克服这一挑战。为此，本研究考虑使用一种阿司匹林金属配合物，即铜酰水杨酸（CAS），作为一种抗真菌剂。此外，本研究还研究了该化合物对巨噬细胞功能的影响。药敏结果表明，隐球菌细胞易受 CAS 的影响（呈剂量依赖性），这可能通过破坏隐球菌细胞膜来抑制其生长。有趣的是，当 CAS 与氟康唑或两性霉素 B 联合使用时，观察到协同作用。此外，CAS 不会对巨噬细胞的生长或代谢活性产生负面影响；相反，它使这些免疫细胞对产生干扰素γ和白细胞介素 6 敏感，而这反过来又可能有助于吞噬隐球菌细胞。与我们的阿司匹林数据相比，CAS 被证明在杀死隐球菌细胞方面更有效（基于药敏结果），对巨噬细胞的毒性更小（基于生长抑制结果）。综上所述，CAS 可能是一种更好的抗真菌药物，与阿司匹林相比，它可能带来更好的治疗效果。
