Kakuol

Pest Manag. Sci., 2005, 61(8):821-5.

Isolation and antifungal activity of kakuol, a propiophenone derivative from Asarum sieboldii rhizome.[Pubmed: 15846774 ]

METHODS AND RESULTS:
An antifungal substance active against Colletotrichum orbiculare (Berk & Mont) Arx was isolated from the methanol extracts of Asarum sieboldii (Miq) Maek rhizomes. High-resolution MS, NMR and UV spectral data confirmed that the antifungal substance is Kakuol, 2-hydroxy-4,5-methylenedioxypropiophenone. Colletotrichum orbiculare was most sensitive to Kakuol, with MIC of 10 microg ml(-1). Kakuol also completely inhibited the mycelial growth of Botrytis cinerea Pers ex Fr and Cladosporium cucumerinum Ellis & Arthur at 50 microg ml(-1) and 30 microg ml(-1), respectively. However, no antimicrobial activity was found against yeast and bacteria even at 100 microg ml(-1). Kakuol exhibited a protective activity against the development of anthracnose disease on cucumber plants. The control efficacy of Kakuol against the anthracnose disease was in general somewhat less than that of the commercial fungicide chlorothalonil.
CONCLUSIONS:
This is the first report to demonstrate in vitro and in vivo antifungal activity of Kakuol against C. orbiculare infection.

Arch. Biochem. Biophys., 2013, 530(1):7-12.

A derivative of the natural compound kakuol affects DNA relaxation of topoisomerase IB inhibiting the cleavage reaction.[Pubmed: 23262316 ]

Topoisomerases IB are anticancer and antimicrobial targets whose inhibition by several natural and synthetic compounds has been documented over the last three decades.
METHODS AND RESULTS:
Here we show that Kakuol, a natural compound isolated from the rhizomes of Asarum sieboldii, and a derivative analogue are able to inhibit the DNA relaxation mediated by the human enzyme. The analogue is the most efficient one and the inhibitory effect is enhanced upon pre-incubation with the enzyme. Analysis of the different steps of the catalytic cycle indicates that the inhibition occurs at the cleavage level and does not prevent DNA binding.
CONCLUSIONS:
Molecular docking shows that the compound preferentially binds near the active site at the bottom of the catalytic residue Tyr723, providing an atomistic explanation for its inhibitory activity.