Centre for Biotechnology, Maharshi Dayanand University, Rohtak, Haryana, India.
Curr Pharm Biotechnol. 2013;14(2):226-32.
There is continuous emergence of resistant strains which leads to urgent need to discover new antifungal agents. The investigation of adjunctive agents for antifungal activity might help to optimize the therapy for Invasive Aspergillosis (IA). The chelating agents Ethylenediamine Tetraacetic Acid (EDTA) & Disodium salt of EDTA (DiEDTA) as adjunct to antifungal drugs have been investigated against 8 pathogenic isolates of Aspergillus spp. The MIC (Minimum Inhibitory Concentration) found by DDA (Disc Diffusion Assay) is 7.50-15.0 μg/disc; by MDA (Microbroth Dilution Assay) is 30.0-49.13 μg/ml & SGIA (Spore germination Inhibition Assay) is 30.0-49.13 μg/ml. Moreover, these agents did not show any toxicity up to a concentration of 312.5 μg/ml. The antifungal activity is also confirmed by another method i.e time kill curve analysis. While these agents were ten times less active than gold standard drug (Amphotericin B; AmpB) but eight times less toxic than AmpB. This leads to preliminary investigation of in vitro combination of chelating agents with antifungal drugs (Polyenes & Azoles) by DDA. These combinations showed a significant increase in zone of inhibition in contrast to single drug used. This preliminary work with chelating agents suggest that EDTA as an enhancing agent with antifungal properties in combination with antifungal drugs can be used in pharmaceutical preparations. Further investigation is in progress.
不断出现的耐药菌株导致急需发现新的抗真菌药物。研究抗真菌活性的辅助剂可能有助于优化侵袭性曲霉病 (IA) 的治疗。研究了乙二胺四乙酸 (EDTA) 和 EDTA 的二钠盐 (DiEDTA) 等螯合剂作为抗真菌药物的佐剂,以对抗 8 种致病性曲霉属分离株。DDA(圆盘扩散测定)发现的 MIC(最小抑菌浓度)为 7.50-15.0 μg/disc;MDA(微量肉汤稀释测定)为 30.0-49.13 μg/ml 和 SGIA(孢子萌发抑制测定)为 30.0-49.13 μg/ml。此外,这些试剂在高达 312.5 μg/ml 的浓度下均没有显示出任何毒性。另一种方法即时间杀伤曲线分析也证实了这些试剂的抗真菌活性。虽然这些试剂的活性比金标准药物(两性霉素 B;AmpB)低十倍,但毒性比 AmpB 低八倍。这导致通过 DDA 对螯合剂与抗真菌药物(多烯类和唑类)的体外联合进行初步研究。与单独使用药物相比,这些组合显示出抑制区显著增加。螯合剂的初步研究表明,EDTA 作为一种具有抗真菌特性的增强剂,与抗真菌药物联合使用,可以用于药物制剂。进一步的研究正在进行中。