Naghibione; A Novel Sesquiterpenoid with Antiplasmodial Effect from Dorema hyrcanum Koso-Pol. Root, a Plant Used in Traditional Medicine

Some Dorema species are used in Persian traditional medicine. In the present study the total extract from the roots of Dorema hyrcanum Koso-Pol. was investigated for its in vitro (pLDH assay) and in vivo (Peters’ 4-days suppressive test) antiplasmodial effects and assessed for cytotoxicity against the normal cell line MDBK (MTT test). The IC50 values for a chloroquine- sensitive (3D7) and a chloroquine- resistance (K1) strain of Plasmodium falciparum were 28.64 and 9.79 µg/ml, respectively. The inhibition percentage of the rodent parasite, Plasmodium berghei, on day 4 in mice was 77.9% and IC50 value on Madin–Darby bovine kidney cells (MDBK cells) was 59.84µg/ml. The total extract was subjected to a bioassay-guided fractionation protocol based on the in vivo model which resulted in the isolation of an acetophenon (compound 1), one new sesquiterpenoid, 1(2-hydroxy-4-methoxy)- 3,7,11- trimethyl-3-vinyl-6(E), 10 dodecadiene- 1- dione (compound 2) and two known sesquiterpenoid derivatives (compounds 3, 4). Their structures were elucidated by spectroscopic analysis, including 1D and 2D NMR experiments and ESI-MS. All compounds were evaluated for in vivo antiplasmodial effect and the results revealed that compound 2 showed good suppression activity, inhibiting 68.1 % of the parasite growth.