title: Synthesis, Antifungal Activity, and Biocompatibility of Novel 1,4-Diazabicyclo[2.2.2]Octane (DABCO) Compounds and DABCO-Containing Denture Base Resins.
abstract: The fungal pathogenCandida albicanscauses 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 severalCandidaspecies 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 surfaceC. albicansbiofilm 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 againstCandida-associated denture stomatitis.
authors.affiliation: Department of Periodontics, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Herman
authors.affiliation: Department of Comprehensive Dentistry and Biomaterials, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
authors.forename: Yapin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Oral Biology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Lilly
authors.affiliation: Department of Anatomy and Cell Biology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Lallier
authors.affiliation: Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Peters
authors.affiliation: Department of Comprehensive Dentistry and Biomaterials, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
authors.forename: Suleiman
authors.initials: S
authors.lastname: Hamdan
authors.affiliation: Department of Comprehensive Dentistry and Biomaterials, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Oral Biology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Fidel
authors.affiliation: Department of Prosthodontics, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA mnover@lsuhsc.edu.
authors.forename: Mairi C
authors.initials: MC
authors.lastname: Noverr
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D003819:Denture Bases; D008826:Microbial Sensitivity Tests; D010879:Piperazines / Q000494:pharmacology*; D013282:Stomatitis, Denture / Q000382:microbiology
chemical_list: D000935:Antifungal Agents; D010879:Piperazines; C007306:triethylenediamine
keywords: Candida albicans; antifungal agents; antifungal material; antifungal susceptibility testing; denture stomatitis