Drug Discov Ther. 2014;8(6):238-244. (DOI: 10.5582/ddt.2014.01045)

Several herbal compounds in Okinawa plants directly inhibit the oncogenic/aging kinase PAK1.

Nguyen BCQ, Taira N, Tawata S


The p21-activated kinase 1 (PAK1) is emerging as a promising therapeutic target, and the search for blockers of this oncogenic/aging kinase would be potentially useful for the treatment of various diseases/disorders in the future. Here, we report for the first time the anti-PAK1 activity of compounds derived from three distinct Okinawa plants. 5,6-Dehydrokawain (DK) and dihydro-5,6-dehydrokawain (DDK) from alpinia inhibited directly PAK1 more strongly than mimosine and mimosinol from leucaena. Cucurbitacin I isolated from bitter gourd/melon also exhibited a moderate anti-PAK1 activity. Hispidin, a metabolite of DK, strongly inhibited PAK1 with the IC50 = 5.7 μM. The IC50 of three hispidin derivatives (H1-3) for PAK1 inhibition ranges from 1.2 to 2.0 μM, while mimosine tetrapeptides [mimosine-Phe-Phe-Tyr (MFFY) and mimosine-Phe-Trp-Tyr (MFWY)] inhibit PAK1 at nanomolar level (IC50 of 0.13 and 0.60 μM, respectively). Thus, we hope these derivatives of hispidin and mimosine could be used as potential leading compounds for developing far more potent anti-PAK1 drugs which would be useful for clinical application in the future.

KEYWORDS: p21-activated kinase 1, 5,6-dehydrokawain, dihydro-5,6-dehydrokawain, mimosine, cucurbitacin I

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