Gandra Rafael M, Mc Carron Pauraic, Fernandes Mariana F, Ramos Lívia S, Mello Thaís P, Aor Ana Carolina, Branquinha Marta H, McCann Malachy, Devereux Michael, Santos André L S
Laboratório de Investigação de Peptidases, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de JaneiroRio de Janeiro, Brazil.
Programa de Pós-Graduação em Bioquímica, Instituto de Química, Universidade Federal do Rio de JaneiroRio de Janeiro, Brazil.
Front Microbiol. 2017 Jul 11;8:1257. doi: 10.3389/fmicb.2017.01257. eCollection 2017.
var. and , which form the complex, are emerging etiologic agents of fungal infections known to be resistant to the most commonly used antifungals. The well-established anti- potential of metal complexes containing 1,10-phenanthroline (phen) ligands encouraged us to evaluate different copper(II), manganese(II), and silver(I) phen chelates for their ability to inhibit planktonic growth and biofilm of species complex. Two novel coordination complexes, {[Cu(3,6,9-tdda)(phen)].3HO.EtOH} and [Ag(3,6,9-tdda)(phen)].EtOH (3,6,9-tddaH = 3,6,9-trioxaundecanedioic acid), were synthesized in a similar fashion to the other, previously documented, sixteen copper(II), manganese(II), and silver(I) chelates employed herein. Three isolates of each species complex were used and the effect of the metal chelates on viability was determined utilizing the CLSI standard protocol and on biofilm-growing cells using the XTT assay. Cytotoxicity of the chelates was evaluated by the MTT assay, employing lung epithelial cells. The majority of the metal chelates were capable of interfering with the viability of planktonic-growing cells of all the fungal isolates. The silver complexes were the most effective drugs (overall geometric mean of the minimum inhibitory concentration (GM-MIC) ranged from 0.26 to 2.16 μM), followed by the manganese (overall GM-MIC ranged from 0.87 to 10.71 μM) and copper (overall GM-MIC ranged from 3.37 to >72 μM) chelates. The manganese chelates (CC values ranged from 234.51 to >512 μM) were the least toxic to the mammalian cells, followed by the silver (CC values ranged from 2.07 to 13.63 μM) and copper (CC values ranged from 0.53 to 3.86 μM) compounds. When tested against mature biofilms, the chelates were less active, with MICs ranging from 2- to 33-fold higher levels when compared to the planktonic MIC counterparts. Importantly, manganese(II), copper(II), and silver(I) phen chelates are relatively cheap and easy to synthesize and they offer significant antifungal chemotherapeutic potential for the treatment of highly resistant pathogens.
变种 和 ，它们形成 复合物，是已知对最常用抗真菌药物耐药的真菌感染的新兴病原体。含有1,10 - 菲咯啉（phen）配体的金属配合物具有公认的抗 潜力，这促使我们评估不同的铜（II）、锰（II）和银（I）菲咯啉螯合物抑制 菌种复合物浮游生长和生物膜形成的能力。以与本文中使用的其他先前记录的十六种铜（II）、锰（II）和银（I）螯合物类似的方式合成了两种新型配位复合物，{[Cu(3,6,9 - tdda)(phen)].3H₂O.EtOH}和[Ag(3,6,9 - tdda)(phen)].EtOH（3,6,9 - tddaH = 3,6,9 - 三氧杂十一烷二酸）。使用每种 菌种复合物的三个分离株，并利用CLSI标准方案测定金属螯合物对生存力的影响，使用XTT测定法测定对生物膜生长细胞的影响。通过MTT测定法，使用肺上皮细胞评估螯合物的细胞毒性。大多数金属螯合物能够干扰所有真菌分离株浮游生长细胞的生存力。银配合物是最有效的药物（最小抑菌浓度的总体几何平均值（GM - MIC）范围为0.26至2.16 μM），其次是锰（总体GM - MIC范围为0.87至10.71 μM）和铜（总体GM - MIC范围为3.37至>72 μM）螯合物。锰螯合物（CC值范围为234.51至>512 μM）对哺乳动物细胞毒性最小，其次是银（CC值范围为2.07至13.63 μM）和铜（CC值范围为0.53至3.86 μM）化合物。当针对成熟生物膜进行测试时，螯合物的活性较低，与浮游MIC对应物相比，MIC值高出2至33倍。重要的是，锰（II）、铜（II）和银（I）菲咯啉螯合物相对便宜且易于合成，它们为治疗高度耐药病原体提供了显著的抗真菌化疗潜力。
