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Anti-microbial and anti-biofilm activities of combined chelerythrine-sanguinarine and mode of action against Candida albicans and Cryptococcus neoformans in vitro. 2020

Weidong Qian, and Min Yang, and Xinchen Li, and Zhaohuan Sun, and Yongdong Li, and Xuejun Wang, and Ting Wang
School of Food and Biological Engineering, Shaanxi University of Science and Technology, Xi'an, 710021, PR China; Biological and Chemical Engineering Institute, Nanyang Institute of Technology, Nanyang, 473004, PR China.

The increasing prevalence of fungal infections coupled with emerging drug resistance has stimulated an urgent need to explore new and effective antifungal agents. Sanguinarine and chelerythrine constitute alkaloids that have exhibited antifungal activities. However, the effects of a 1:1 mixture of these agents against Candida albicans and Cryptococcus neoformans have remained largely unexplored. The purpose of this study was to assess the anti-fungal and anti-biofilm efficacy of combined chelerythrine-sanguinarine against C. albicans and C. neoformans in vitro. Combined chelerythrine-sanguinarine inhibited C. albicans and C. neoformans growth with minimum inhibitory concentrations (MICs) of 2 and 16 μg/mL, respectively, and effectively inhibited adhesion and biofilm formation of these pathogens at minimum biofilm inhibitory concentrations of 1 and 8 μg/mL. Notably, the mixture significantly eradicated mature C. albicans and C. neoformans biofilms at 8 and 128 μg/mL, respectively. In particular, the mixture was found to disrupt cell membrane integrity and enhance penetration of antibiotics into fungal cells, suggesting its antifungal mode of action. Hence, combined chelerythrine-sanguinarine shows promise as a potential anti-fungal and anti-biofilm agent for the management of serious infections caused by C. albicans and C. neoformans.

UI MeSH Term Description Entries
D007546 Isoquinolines A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D010316 Particle Size Relating to the size of solids. Particle Sizes,Size, Particle,Sizes, Particle
D002176 Candida albicans A unicellular budding fungus which is the principal pathogenic species causing CANDIDIASIS (moniliasis). Candida albicans var. stellatoidea,Candida stellatoidea,Dematium albicans,Monilia albicans,Myceloblastanon albicans,Mycotorula albicans,Parasaccharomyces albicans,Procandida albicans,Procandida stellatoidea,Saccharomyces albicans,Syringospora albicans
D003455 Cryptococcus neoformans A species of the fungus CRYPTOCOCCUS. Its teleomorph is Filobasidiella neoformans. Blastomyces neoformans,Debaryomyces neoformans,Filobasidiella neoformans,Lipomyces neoformans,Saccharomyces neoformans,Torula neoformans,Torulopsis neoformans,Cryptococcus neoformans var. grubii
D000935 Antifungal Agents Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues. Anti-Fungal Agents,Antifungal Agent,Fungicides, Therapeutic,Antibiotics, Antifungal,Therapeutic Fungicides,Agent, Antifungal,Anti Fungal Agents,Antifungal Antibiotics
D013499 Surface Properties Characteristics or attributes of the outer boundaries of objects, including molecules. Properties, Surface,Property, Surface,Surface Property
D053119 Benzophenanthridines Compounds of four rings containing a nitrogen. They are biosynthesized from reticuline via rearrangement of scoulerine. They are similar to BENZYLISOQUINOLINES. Members include chelerythrine and sanguinarine.
D018441 Biofilms Encrustations formed from microbes (bacteria, algae, fungi, plankton, or protozoa) embedded in an EXTRACELLULAR POLYMERIC SUBSTANCE MATRIX that is secreted by the microbes. They occur on body surfaces such as teeth (DENTAL DEPOSITS); inanimate objects, and bodies of water. Biofilms are prevented from forming by treating surfaces with DENTIFRICES; DISINFECTANTS; ANTI-INFECTIVE AGENTS; and anti-fouling agents. Biofilm

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