Antitrypanosomal Quinoline Alkaloids from the Roots of Waltheria indica

Abstract

Chemical investigation of the dichloromethane root extract of Waltheria indica led to the isolation and characterization of 10 quinoline alkaloids, namely, 8-deoxoantidesmone (1), waltheriones E-L (2-9), and antidesmone (10). Among these, compounds 2-9 have not yet been described in the literature. Their chemical structures were established by means of spectroscopic data interpretation including (1)H and (13)C NMR, HSQC, HMBC, COSY, and NOESY experiments and UV, IR, and HRESIMS. The absolute configurations of the compounds were established by comparison of experimental and TDDFT-calculated ECD spectra. In addition, the isolated constituents were evaluated for their in vitro antitrypanosomal activity. Compounds 4, 5, and 8 showed potent and selective growth inhibition toward Trypanosoma cruzi with IC50 values between 0.02 and 0.04 μM. Cytotoxicity for mouse skeletal L-6 cells was also determined for these compounds.

Compounds from African Medicinal Plants with Activities against Protozoal Diseases: Schistosomiasis, Trypanosomiasis and Leishmaniasis

“…[99][100][101][102][103] The dichloromethane root extract showed activities against T. cruzi (IC50 = 0.74 μg/mL), T. b. brucei (2.3% survival at 20 μg/mL) and T. b. rhodesiense (IC50 = 17.4 μg/mL). 98 With the exception of waltherione L (26), with a slightly higher IC50 (3.1 μM), the isolated compounds all displayed potent growth inhibition toward the amastigote form of T. cruzi (the Tulahuen C4 strain), with IC50 values lower than that of the reference drug benznidazole (IC50 = 2.9 μM). Structureactivity relationships (SARs) provide suggestions that, a methoxy group, bound to the nitrogen atom is important for activity (e.g.…”

“…98 This plant is used in traditional medicine for the treatment of several ailments, including malaria. [99][100][101][102][103] The dichloromethane root extract showed activities against T. cruzi (IC50 = 0.74 μg/mL), T. b. brucei (2.3% survival at 20 μg/mL) and T. b. rhodesiense (IC50 = 17.4 μg/mL).…”

Prediction of the Passive Intestinal Absorption of Medicinal Plant Extract Constituents with the Parallel Artificial Membrane Permeability Assay (PAMPA)

“…lobata, and A. archangelica) were selected. The extracts were prepared in order to insure that they contain the metabolites that are ingested when the medicinal plant is orally taken: a methanolic extract of the fruits from A. archangelica mostly composed of furanocoumarins [43,44], a decoction of aerial parts of W. indica containing quinoline alkaloids [33], and a decoction of roots of P. montana var. lobata with flavonoid glycosides [35].…”

“…A complementary LC-MS-based dereplication indicated that the more lipophilic NPs belong to the quinoline alkaloids waltherione C, E, and G and to flavonoid aglycones, whereas the more polar group of constituents included cyclopeptide alkaloids adouetin X and Y [33,34]. The effective passive permeability values of the pharmacologically active waltheriones C, E, and G were calculated and such compounds were found to have medium permeability (l " Fig.…”

“…Phellopterin (≥ 99 %) and isoimperatorin (≥ 98%) was purchased from PhytoLab GmbH. Waltherione A, C, E, and G were isolated and dereplicated from W. indica as previously described (minimum purity of 95 %) [33,34]. (50 g) were powdered and extracted with 0.5 L of boiling water for 1 h. After filtration, the aqueous extract was evaporated and concentrated to 100 mL.…”