Trypanocidal Terpenoids from Laurus nobilis L.

Abstract

Trypanosoma cruzi, a parasitic protozoan of Zoomastigophoria, is the etiologic agent of Chagas' disease which is endemic in Central and South America.1) In our screening work on medicinal plants used in Asian counties for trypanocidal activity, extracts of the dried leaves of Laurus nobilis L. (Lauraceae) showed strong trypanocidal activity against epimastigotes of T. cruzi. Leaves of L. nobilis are used as a spice known as laurel or bay leaf. They are also used as a folk medicine for rheumatism and scabies.2) Although some biological activities such as inhibition of elevation of blood ethanol level in ethanol-loaded rat, 3) inhibition of nitric oxide production in lipopolysaccharide-activated mouse peritoneal macrophages, 4) induction of glutathione Stransferase activity, 5) and nematocidal activity 6) were reported for the constituents of L. nobilis, nothing has been reported on anti-protozoan constituents of this plant. Here, we report the isolation and identification of trypanocidal constituents of L. nobilis. Results and DiscussionDried leaves of Laurus nobilis were successively extracted with hexane, CHCl 3 and MeOH, and each extract was tested for anti-trypanosomal effect by the HeLa cell infection assay.7) As the CHCl 3 and MeOH extracts inhibited infection and proliferation of T. cruzi, and the MeOH extract formed the major part of the extracts, the MeOH extract was further fractionated under the guidance of in vitro trypanocidal activity against epimastigotes of T. cruzi.8) The MeOH extract was suspended in aqueous MeOH and fractionated into hexane soluble, AcOEt soluble, and water soluble fractions. Since the AcOEt soluble fraction showed the strongest activity, it was fractionated by silica gel column chromatography to give three trypanocidal compounds (1-3). These compounds were also isolated from the CHCl 3 extracts.Compounds 1 and 2 were obtained as colorless needles from hexane, mp 58-60°C, and as a colorless oil, respectively. The 1 H-and 13 C-NMR spectra indicated that both compounds were guaiane-type sesquiterpene with three exocyclic methylene moieties. Based on comparisons of the spectral data with those reported, compounds 1 and 2 were identified with dehydrocostus lactone (1) 9) and zaluzanin D (2), 10) H-detected heteronuclear multiple quantum coherence (HMQC) and heteronuclear multiple bond connectivity (HMBC) spectra (Fig. 1) revealed the structure to be 1-hydroperoxy-pmenthan-2-en-8-ol acetate. Treatment of 3 with PPh 3 gave an acetoxy alcohol 4, which showed oxygen-bearing carbons at d C 67.0 (C-1) and d C 84.4 (C-8). This confirmed that 3 had a hydroperoxy and an acetoxy group at positions 1 and 8, respectively. Since nuclear Overhauser effect (NOE) experiments did not provide conclusive stereochemical information, the stereochemistry of 3 was determined by chemical correlations. Photo C-NMR spectra of 7 were identical with those of the diol 8, which was derived from 3 by alkaline hydrolysis followed by reduction with PPh 3 . 12)This result established that the relative stereochemi...

Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C NMR spectral data and biological properties

“…The minimum lethal concentrations of these compounds against epimastigotes of T. cruzi were 7 lM and 25 lM, respectively (Asaruddin et al, 2003). Also dehydrocostus lactone (142) and zaluzanin D (148) showed lethal activity against epimastigotes of T. cruzi at concentrations of 6.3 and 2.5 lM, respectively (Uchiyama et al, 2002).…”

Screening of Southeastern BrazilianMikania. Species onTrypanosoma cruzi.

“…Several sesquiterpene lactones have been reported to show trypanocidal activity. Results suggest the mechanism of action of this group of compounds relies on covalent bond formation of the a,b-unsaturated c-lactone moiety with nucleophiles that are essential for the life of the parasite (Uchiyama et al, 2002).…”

An examination of the Antimicrobial and Anticancer Properties of Khaya senegalensis (Desr.) A. Juss. Bark Extracts

“…33 Our studies demonstrate that K. senegalensis bark also possesses anti-Giardial activity. Whilst, further studies are required to identify the active component(s), previous studies have identified several similar terpenoids in plants 49 and marine sponges 50 which inhibit the growth of parasitic protozoans. The former of these studies is of particular note as it correlates trypanocidal activity with similar sesquiterpenoid lactones as those detected in our study.…”