2-amino-nonyl-6-methoxyl-tetralin muriate activity against Candida albicans augments endogenous reactive oxygen species production --a microarray analysis study.
Candida infections have become an increasingly significant problem, mainly because of the widespread nature of Candida and drug resistance. There is an urgent need to develop new classes of drugs for the treatment of opportunistic Candida infections, especially in medically complex patients. Previous studies have confirmed that 2-amino-nonyl-6-methoxyl-tetralin muriate (10b) possesses powerful antifungal activity in vitro against Candia albicans. To clarify the underlying action mechanism, an oligonucleotide microarray study was performed in C. albicans SC5314 without and with 10b treatment. The analytical results showed that energy metabolism-related genes, including glycolysis-related genes (PFK1, CDC19 and HXK2), fermentation-related genes (PDC11, ALD5 and ADH1) and respiratory electron transport chain-related genes (CBP3, COR1 and QCR8), were downregulated significantly. Functional analysis revealed that 10b treatment increased the generation of endogenous reactive oxygen species, and decreased mitochondrial membrane potential, ubiquinone-cytochrome c reductase (complex III) activity and intracellular ATP levels in C. albicans SC5314. Also, addition of the antioxidant ascorbic acid reduced the antifungal activity of 10b significantly. These results suggest that mitochondrial aerobic respiration shift and endogenous reactive oxygen species augmentation might contribute to the antifungal activity of 10b against C. albicans. This information may prove to be useful for the development of new strategies to treat Candida infections.
Drug Development Center, School of Pharmacy, Second Military Medical University, Shanghai, China.
Rong Mei
RM
Liang
Xiao Lan
XL
Yong
Yun Ping
YP
Jiang
Yong Hong
YH
Tan
Bao Di
BD
Dai
Shi Hua
SH
Wang
Ting Ting
TT
Hu
Xi
X
Chen
Nan
N
Li
Zhao Hui
ZH
Dong
Xiao Chun
XC
Huang
Jun
J
Chen
Yong Bing
YB
Cao
Yuan Ying
YY
Jiang
D000255:Adenosine Triphosphate / Q000378:metabolism; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002176:Candida albicans / Q000166:cytology / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism*; D002177:Candidiasis / Q000188:drug therapy; D019069:Cell Respiration / Q000187:drug effects; D025141:Drug Resistance, Fungal / Q000187:drug effects; D042967:Electron Transport Complex I / Q000187:drug effects / Q000502:physiology; D014450:Electron Transport Complex III / Q000187:drug effects / Q000502:physiology; D020869:Gene Expression Profiling; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D046228:Microarray Analysis / Q000379:methods*; D008826:Microbial Sensitivity Tests; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
C550315:2-amino-nonyl-6-methoxyl-tetralin muriate; D000935:Antifungal Agents; D017382:Reactive Oxygen Species; D013764:Tetrahydronaphthalenes; D000255:Adenosine Triphosphate; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III