Isodiospyrin

Phytother Res. 2000 Mar;14(2):112-7.

Antibacterial activity of diospyrin, isodiospyrin and bisisodiospyrin from the root of Diospyros piscatoria (Gurke) (Ebenaceae).[Pubmed: 10685108 ]

METHODS AND RESULTS:
Two dimeric naphthoquinones, diospyrin and Isodiospyrin, isolated from the root of Diospyros piscatoria (Gurke), a common ingredient in several folk medicines, have been shown to have a broad spectrum of antibacterial activity. The minimum inhibitory concentrations (MICs) of diospyrin against Streptococcus pyogenes ATCC 12344 and Streptococcus pneumoniae ATCC 33400 ranged from 1.56 to 50 microg/mL. While those against Salmonella choleraesuis serotype typhi (S. typhi), ATCC 6539 and Mycobacterium chelonae ATCC 19977 were between 25 and 100 microg/mL. Isodiospyrin was more active than its racemic isomer diospyrin. The MICs against Gram-positive bacteria ranged from 0.78 to 50 microg/mL. While those against Pseudomonas aeruginosa ATCC 15443 and S. typhi ranged from 50 to 100 microg/mL. The MIC for M. chelonae was between 6.25 and 25 microg/mL. MICs were found to increase with the concentration of cells used for the inoculum. The MICs for Bacillus subtilis ATCC 6633 increased up to the highest concentration of cells tested. The same phenomenon was observed on M. chelonae, but with better effect in the latter.
CONCLUSIONS:
The kinetics of bacteria studies against both B. subtilis and M. chelonae increases with increasing concentration of Isodiospyrin tested. Two tetrameric forms of plumbagin were isolated. The naphthoquinone bisIsodiospyrin, gave MIC values between 300 and 400 micro g/mL. The second, as yet unidentified tetramer, was not active at 500 micro g/mL.

Chem Biodivers. 2011 Dec;8(12):2331-40.

Antifungal metabolites from the roots of Diospyros virginiana by overpressure layer chromatography.[Pubmed: 22162171 ]

METHODS AND RESULTS:
A preparative overpressure layer chromatography (OPLC) method was successfully used for the separation of two new natural compounds, 4-hydroxy-5,6-dimethoxynaphthalene-2-carbaldehyde (1) and 12,13-didehydro-20,29-dihydrobetulin (2) together with nine known compounds, including 7-methyljuglone (3), diospyrin (4), Isodiospyrin (5), shinanolone (6), lupeol (7), betulin (8), betulinic acid (9), betulinaldehyde (10), and ursolic acid (11) from the acetone extract of the roots of Diospyros virginiana. Their identification was accomplished by 1D- and 2D-NMR spectroscopy and HR-ESI-MS methods. All the isolated compounds were evaluated for their antifungal activities against Colletotrichum fragariae, C. gloeosporioides, C. acutatum, Botrytis cinerea, Fusarium oxysporum, Phomopsis obscurans, and P. viticola using in vitro micro-dilution broth assay.
CONCLUSIONS:
The results indicated that compounds 3 and 5 showed high antifungal activity against P. obscurans at 30 μM with 97.0 and 81.4% growth inhibition, and moderate activity against P. viticola (54.3 and 36.6%). It appears that an optimized OPLC system offers a rapid and efficient method of exploiting bioactive natural products.

Biochem Pharmacol. 2003 Nov 15;66(10):1981-91.

Isodiospyrin as a novel human DNA topoisomerase I inhibitor.[Pubmed: 14599556]

Isodiospyrin is a natural product from the plant Diospyros morrisiana, which consists of an asymmetrical 1,2-binaphthoquinone chromophore.
METHODS AND RESULTS:
Isodiospyrin exhibits cytotoxic activity to tumor cell lines but very little is known about its cellular target and mechanism of action. Unlike the prototypic human topoisomerase I (htopo I) poison camptothecin, Isodiospyrin does not induce htopo I-DNA covalent complexes. However, Isodiospyrin antagonizes camptothecin-induced, htopo I-mediated DNA cleavage. Binding analysis indicated that Isodiospyrin binds htopo I but not DNA. These results suggest that Isodiospyrin inhibits htopo I by direct binding to htopo I, which limits htopo I access to the DNA substrate. Furthermore, Isodiospyrin exhibits strong inhibitory effect on the kinase activity of htopo I toward splicing factor 2/alternate splicing factor in the absence of DNA.
CONCLUSIONS:
Thus, these findings have important implications on naphthoquinone and its derivatives' cellular mode of actions, i.e. these novel DNA topoisomerase I inhibitors can prevent both DNA relaxation and kinase activities of htopo I.