Lippert Rainer, Vojnovic Sandra, Mitrovic Aleksandra, Jux Norbert, Ivanović-Burmazović Ivana, Vasiljevic Branka, Stankovic Nada
Friedrich-Alexander University Erlangen-Nuremberg, Department of Chemistry & Pharmacy, Egerlandstr. 1, 91058 Erlangen, Germany.
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, PO Box 23, 11000 Belgrade, Serbia.
Bioorg Med Chem Lett. 2014 Aug 1;24(15):3506-11. doi: 10.1016/j.bmcl.2014.05.061. Epub 2014 May 27.
Ferrocene-substituted porphyrin RL-91 exhibits antifungal activity against opportune human pathogen Candida albicans. RL-91 efficiently inhibits growth of both planktonic C. albicans cells and cells within biofilms without photoactivation. The minimal inhibitory concentration for plankton form (PMIC) was established to be 100 μg/mL and the same concentration killed 80% of sessile cells in the mature biofilm (SMIC80). Furthermore PMIC of RL-91 efficiently prevents C. albicans biofilm formation. RL-91 is cytotoxic for human fibroblasts in vitro in concentration of 10 μg/mL, however it does not cause hemolysis in concentrations of up to 50 μg/mL. These findings open possibility for application of RL-91 as an antifungal agent for external antibiofilm treatment of medical devices as well as a scaffold for further development of porphyrin based systemic antifungals.
二茂铁取代的卟啉RL - 91对人类机会致病菌白色念珠菌具有抗真菌活性。RL - 91能有效抑制浮游态白色念珠菌细胞以及生物膜内细胞的生长，且无需光激活。浮游态白色念珠菌的最小抑菌浓度（PMIC）确定为100μg/mL，相同浓度可杀死成熟生物膜中80%的固着细胞（SMIC80）。此外，RL - 91的PMIC能有效阻止白色念珠菌生物膜的形成。RL - 91在体外对人成纤维细胞具有细胞毒性，浓度为10μg/mL，但在浓度高达50μg/mL时不会引起溶血。这些发现为RL - 91作为一种用于医疗器械外部抗生物膜治疗的抗真菌剂以及作为基于卟啉的全身性抗真菌药物进一步开发的支架提供了应用可能性。
