Herman Jenny L, Wang Yapin, Lilly Elizabeth A, Lallier Thomas E, Peters Brian M, Hamdan Suleiman, Xu Xiaoming, Fidel Paul L, Noverr Mairi C
Department of Periodontics, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
Department of Comprehensive Dentistry and Biomaterials, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
Antimicrob Agents Chemother. 2017 Mar 24;61(4). doi: 10.1128/AAC.02575-16. Print 2017 Apr.
The fungal pathogen causes a variety of oral infections, including denture stomatitis, which is characterized by inflammation of the oral mucosa in direct contact with dentures and affects a significant number of otherwise healthy denture wearers. While antifungal treatment reduces symptoms, infections are often recurrent. One strategy to address this problem is to incorporate compounds with fungicidal activities into denture materials to prevent colonization. Our laboratory synthesized novel derivatives of 1,4-diazabicyclo[2.2.2]octane (DABCO), which is an organic compound typically used as a catalyst in polymerization reactions. DABCO derivatives with different aliphatic chain lengths (DC16, DC16F, DC18, and C6DC16), as well as methacrylate monomers conjugated to DABCO compounds (DC11MAF and C2DC11MAF), were synthesized and tested for antimicrobial activity. All the compounds exhibited fungicidal activity against several species at concentrations ranging between 2 and 4 μg/ml. Moreover, acrylic denture base resins fabricated to contain 1, 2, or 4 wt% DABCO compounds inhibited surface biofilm formation, as well as fungal growth, in disc diffusion assays. Remarkably, discs (4 wt%) aged for 2 months also exhibited approximately 100% growth-inhibitory activity. While some DABCO compounds exerted intermediate to high cytotoxicity against mammalian oral cell types, DC11MAF and denture base resin discs containing 2 or 4 wt% C2DC11MAF exhibited relatively low cytotoxicity against periodontal ligament (PDL) cell and gingival fibroblast (GF) lines, as well as primary oral epithelial cells. These studies demonstrate that DABCO derivatives can be incorporated into denture materials and exert fungicidal activity with minimal cytotoxicity to mammalian cells. DC11MAF and C2DC11MAF are considered strong candidates as therapeutic or preventive alternatives against -associated denture stomatitis.
真菌病原体可引发多种口腔感染，包括义齿性口炎，其特征为与义齿直接接触的口腔黏膜发生炎症，影响大量原本健康的义齿佩戴者。虽然抗真菌治疗可减轻症状，但感染往往会复发。解决这一问题的一种策略是将具有杀真菌活性的化合物纳入义齿材料中以防止定植。我们实验室合成了1,4 - 二氮杂双环[2.2.2]辛烷（DABCO）的新型衍生物，DABCO是一种通常在聚合反应中用作催化剂的有机化合物。合成了具有不同脂肪链长度的DABCO衍生物（DC16、DC16F、DC18和C6DC16），以及与DABCO化合物共轭的甲基丙烯酸酯单体（DC11MAF和C2DC11MAF），并测试了它们的抗菌活性。所有化合物在2至4μg/ml的浓度范围内对几种真菌均表现出杀真菌活性。此外，在纸片扩散试验中，含1、2或4 wt% DABCO化合物的丙烯酸义齿基托树脂抑制了表面生物膜形成以及真菌生长。值得注意的是，老化2个月的纸片（4 wt%）也表现出约100%的生长抑制活性。虽然一些DABCO化合物对哺乳动物口腔细胞类型具有中度至高细胞毒性，但DC11MAF以及含2或4 wt% C2DC11MAF的义齿基托树脂纸片对牙周膜（PDL）细胞、牙龈成纤维细胞（GF）系以及原代口腔上皮细胞表现出相对较低的细胞毒性。这些研究表明，DABCO衍生物可纳入义齿材料中，并以对哺乳动物细胞最小的细胞毒性发挥杀真菌活性。DC
