ABSTRACT
The MeOH/CH2Cl2 (1:1) extracts of the roots and leaves of Beilschmiedia louisii and B. obscura showed potent antitrypanosomal activity during preliminary screening on Trypanosoma brucei brucei. Phytochemical investigation of these extracts led to the isolation of a mixture of two new endiandric acid derivatives beilschmiedol B (1) and beilschmiedol C (2), and one new phenylalkene obscurene A (3) together with twelve known compounds (4-15). In addition, four new derivatives (11a-11d) were synthesized from compound 11. Their structures were elucidated based on their NMR and MS data. Compounds 5, 6, and 7 were isolated for the first time from the Beilschmiedia genus. Additionally, the NMR data of compound 4 are given here for the first time. The isolates were evaluated for their antitrypanosomal and antimalarial activities against Tb brucei and the Plasmodium falciparum chloroquine-resistant strain Pf3D7 in vitro, respectively. From the tested compounds, the mixture of new compounds 1 and 2 exhibited the most potent antitrypanosomal activity in vitro with IC50 value of 4.91 µM.
Subject(s)
Anti-Infective Agents/analysis , Antimalarials/pharmacology , Antiparasitic Agents/pharmacology , Carboxylic Acids/chemistry , Lauraceae/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Cell Survival/drug effects , Chloroquine/pharmacology , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Mass Spectrometry , Microbial Sensitivity Tests , Molecular Structure , Plant Leaves/chemistry , Plant Roots/chemistry , Plasmodium falciparum/drug effects , Trypanosoma brucei brucei/drug effectsABSTRACT
Urease enzyme (UE) has been reported to be a potent virulence factor for Helicobacter pylori (HP) bacteria indicated to be responsible for various gastrointestinal diseases. Therefore, the spread of HP, currently regarded by the World Health Organization as a class 1 carcinogen, could be better controlled by targeting UE. It is in this line that we have synthesized three new derivatives (2-4) of the naturally occurring olean-12-en-3-one (1), which was previously isolated from the figs of Ficus vallis-choudae Delile (Moraceae). Among the synthesized compounds, 3 and 4 contain an indole moiety. Their structures were unambiguously assigned by spectroscopic and spectrometric techniques (1D-NMR, 2D-NMR and MS). The starting material and the synthesized compounds were screened for UE inhibition activity, and showed significant activities with IC50 values ranging from 14.5 to 24.6 µM, with compound (1) being the most potent as compared to the positive control thiourea (IC50 = 21.6 µM). Amongst the synthetic derivatives, compound 4 was the most potent (IC50 = 17.9 µM), while the others showed activities close to that of the control. In addition, molecular docking study of target compounds 2-4 was performed in an attempt to explore their binding mode for the design of more potent UE inhibitors.
