Activity of antimicrobial peptide mimetics in the oral cavity: I. Activity against biofilms of Candida albicans.
Naturally occurring antimicrobial peptides hold promise as therapeutic agents against oral pathogens such as Candida albicans but numerous difficulties have slowed their development. Synthetic, non-peptidic analogs that mimic the properties of these peptides have many advantages and exhibit potent, selective antimicrobial activity. Several series of mimetics (with molecular weight < 1000) were developed and screened against oral Candida strains as a proof-of-principle for their antifungal properties. One phenylalkyne and several arylamide compounds with reduced mammalian cytotoxicities were found to be active against C. albicans. These compounds demonstrated rapid fungicidal activity in liquid culture even in the presence of saliva, and demonstrated synergy with standard antifungal agents. When assayed against biofilms grown on denture acrylic, the compounds exhibited potent fungicidal activity as measured by metabolic and fluorescent viability assays. Repeated passages in sub-minimum inhibitory concentration levels did not lead to resistant Candida, in contrast to fluconazole. Our results demonstrate the proof-of principle for the use of these compounds as anti-Candida agents, and their further testing is warranted as novel anti-Candida therapies.
Department of Oral Biology, UMDNJ-New Jersey Dental School, Newark, NJ 07103, USA.
J
J
Hua
R
R
Yamarthy
S
S
Felsenstein
R W
RW
Scott
K
K
Markowitz
G
G
Diamond
D000180:Acrylic Resins; D000480:Alkynes / Q000494:pharmacology; D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects; D018441:Biofilms / Q000187:drug effects*; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects*; D002710:Chlorhexidine / Q000494:pharmacology; D003470:Culture Media; D003764:Dental Materials; D003819:Denture Bases / Q000382:microbiology; D025141:Drug Resistance, Fungal; D004357:Drug Synergism; D015725:Fluconazole / Q000494:pharmacology; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D008970:Molecular Weight; D009055:Mouth / Q000382:microbiology*; D010627:Phenethylamines / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis / Q000494:pharmacology; D012463:Saliva / Q000382:microbiology
D000180:Acrylic Resins; D000480:Alkynes; D000577:Amides; D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D003470:Culture Media; D003764:Dental Materials; C552384:PMX30016; D010627:Phenethylamines; D010636:Phenols; D011743:Pyrimidines; C525734:meta-phenylene ethynylene; D017964:Itraconazole; D015725:Fluconazole; D002710:Chlorhexidine