Dihydrochelerythrine

Nat Prod Res. 2011 Jul;25(11):1082-9.

Inhibitory activity of dihydrosanguinarine and dihydrochelerythrine against phytopathogenic fungi.[Pubmed: 21500094]

The antifungal activities of dihydrosanguinarine and Dihydrochelerythrine, isolated from the leaves of Macleaya microcarpa, were evaluated on 12 plant pathogenic fungi; the two compounds exhibited the highest antifungal activity against Botrytis cinerea Pers.
METHODS AND RESULTS:
Among the 11 tested plant pathogenic fungi in vitro, the two compounds showed the highest antifungal activity against B. cinerea Pers, with 95.16% and 98.32% mycelial growth inhibition at 50 μg mL⁻1, respectively. In addition, the two compounds inhibited spore germination in vitro in a concentration-dependent manner. They also showed potent protective and curative effects against Erysiphe graminis and B. cinerea in vivo.
CONCLUSIONS:
This is the first report on the antifungal activity of dihydrosanguinarine and Dihydrochelerythrine against pathogenic plant fungi.

Vet Parasitol. 2011 Dec 29;183(1-2):8-13.

Antiparasitic efficacy of dihydrosanguinarine and dihydrochelerythrine from Macleaya microcarpa against Ichthyophthirius multifiliis in richadsin (Squaliobarbus curriculus).[Pubmed: 21813242]

Ichthyophthirius multifiliis is a holotrichous protozoan that invades the gills and skin surfaces of fish and can cause morbidity and high mortality in most species of freshwater fish worldwide. The present study was undertaken to investigate the antiparasitic activity of crude extracts and pure compounds from the leaves of Macleaya microcarpa.
METHODS AND RESULTS:
The chloroform extract showed a promising antiparasitic activity against I. multifiliis. Based on these finding, the chloroform extract was fractionated on silica gel column chromatography in a bioactivity-guided isolation affording two compounds showing potent activity. The structures of the two compounds were elucidated as dihydrosanguinarine and Dihydrochelerythrine by hydrogen and carbon-13 nuclear magnetic resonance spectrum and electron ionization mass spectrometry. The in vivo tests revealed that dihydrosanguinarine and Dihydrochelerythrine were effective against I. multifiliis with median effective concentration (EC(50)) values of 5.18 and 9.43 mg/l, respectively. The acute toxicities (LC(50)) of dihydrosanguinarine and Dihydrochelerythrine for richadsin were 13.3 and 18.2mg/l, respectively.
CONCLUSIONS:
The overall results provided important information for the potential application of dihydrosanguinarine and Dihydrochelerythrine in the therapy of serious infection caused by I. multifiliis.

Toxicol In Vitro. 2008 Jun;22(4):1008-17.

Chelerythrine and dihydrochelerythrine induce G1 phase arrest and bimodal cell death in human leukemia HL-60 cells.[Pubmed: 18358694]

A quaternary benzo[c]phenanthridine alkaloid chelerythrine displays a wide range of biological activities including cytotoxicity to normal and cancer cells. In contrast, less is known about the biological activity of Dihydrochelerythrine, a product of chelerythrine reduction.
METHODS AND RESULTS:
We examined the cytotoxicity of chelerythrine and Dihydrochelerythrine in human promyelocytic leukemia HL-60 cells. After 4h of treatment, chelerythrine induced a dose-dependent decrease in the cell viability with IC50 of 2.6 microM as shown by MTT reduction assay. Dihydrochelerythrine appeared to be less cytotoxic since the viability of cells exposed to 20 microM Dihydrochelerythrine for 24h was reduced only to 53%. Decrease in the viability induced by both alkaloids was accompanied by apoptotic events including the dissipation of mitochondrial membrane potential, activation of caspase-9 and -3, and appearance of cells with sub-G1 DNA. Moreover, chelerythrine, but not Dihydrochelerythrine, elevated the activity of caspase-8. A dose-dependent induction of apoptosis and necrosis by chelerythrine and Dihydrochelerythrine was confirmed by annexin V/propidium iodide dual staining flow cytometry. Besides, both alkaloids were found to induce accumulation of HL-60 cells in G1 phase of the cell cycle.
CONCLUSIONS:
We conclude that both chelerythrine and Dihydrochelerythrine affect cell cycle distribution, activate mitochondrial apoptotic pathway, and induce apoptosis and necrosis in HL-60 cells.

J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Dec 15;941:17-24.

Mass spectrometric investigation of chelerythrine and dihydrochelerythrine biotransformation patterns in human hepatocytes.[Pubmed: 24184831]

The quaternary benzo[c]phenanthridine alkaloids (QBAs) are an important subgroup of plant secondary metabolites. Their main representatives, sanguinarine (SG) and chelerythrine (CHE), have pleiotropic biological effects and a wide spectrum of medicinal applications. The biotransformation of SG and CHE has only been partially studied while subsequent oxidative transformation of their dihydro derivates, the main metabolites, is practically unknown. The aim of this study was to characterize the biotransformation of CHE and Dihydrochelerythrine (DHCHE) in detail, with respect to their more extensive biotransformation than SG.
METHODS AND RESULTS:
Phase I as well as phase II biotransformation of both compounds was examined in human hepatocyte suspensions. Liquid chromatography with electrospray-quadrupole time-of-flight mass spectrometry (LC-ESI-QqTOF MS) was used for analysis of the metabolites. Using the LC-ESI-QqTOF MS method, we analyzed and then suggested the putative structures of 11 phase I and 5 phase II metabolites of CHE, and 11 phase I and 6 phase II metabolites of DHCHE. For the most abundant metabolites of CHE, DHCHE and O-demethylated DHCHE, their cytotoxicity on primary cultures of human hepatocytes was analyzed.
CONCLUSIONS:
Both metabolites were nontoxic up to 50μM concentration and this indicates decreasing toxic effects for CHE biotransformation products, i.e. DHCHE and O-demethylated DHCHE.