The anti-Trypanosoma evansi activity of Garcinia hombroniana (seashore mangosteen) leaves aqueous extract was tested on experimentally infected Sprague-Dawley rats. Treatment of infected rats with G. hombroniana extract resulted in a significantly extended post-infection longevity (p
Methanolic extracts of 70 Malaysia plants were screened for their in vitro antitrypanosomal activity using Trypanosome brucei rhodesience, strain STIB 900 and mouse skeletal cell (L-6) in cytotoxicity activity assay. Results indicated that methanol extract from Elephantopus scaber Linn. (E. scaber) possessed the highest value of antitrypanosomal activity with good selectivity index (antitrypanosomal IC50 of 0.22±0.02 μg/ml, SI value of 204.55). Based on these results, E. scaber was chosen for further study by applying bioassay guided fractionation to isolate its antiprotozoal principle. The antiprotozoal principle was isolated from the ethyl acetate partition through solvent fractionation and crystallization process. The isolated active compound 1 was identified as deoxyelephantopin on the basis of its spectral analysis (FTIR, MS, 1D and 2D NMR).
New series of quinoline-based thiadiazole analogs (1-20) were synthesized, characterized by EI-MS, 1H NMR and 13C NMR. All synthesized compounds were subjected to their antileishmanial potential. Sixteen analogs 1-10, 12, 13, 16, 17, 18 and 19 with IC50 values in the range of 0.04 ± 0.01 to 5.60 ± 0.21 µM showed tremendously potent inhibition as compared to the standard pentamidine with IC50 value 7.02 ± 0.09 µM. Analogs 11, 14, 15 and 20 with IC50 8.20 ± 0.35, 9.20 ± 0.40, 7.20 ± 0.20 and 9.60 ± 0.40 µM respectively showed good inhibition when compared with the standard. Structure-activity relationships have been also established for all compounds. Molecular docking studies were performed to determine the binding interaction of the compounds with the active site target.
Dichloromethane extracts of the root bark and stem bark of Kigelia pinnata collected from Zimbabwe exhibited antitrypanosomal activity against Trypanosoma brucei brucei in vitro. Activity-guided fractionation led to the isolation of four naphthoquinones from both the root and stem bark of the plant. The compounds were identified as 2-(1-hydroxyethyl)-naphtho[2,3-b]furan-4,9-quinone (1), isopinnatal (2), kigelinol (3), and isokigelinol (4). Subsequently, the compounds were assessed for antitrypanosomal activity against T. brucei brucei and T. brucei rhodesiense bloodstream form trypomastigotes in vitro. Compound 1 with a furanonaphthoquinone structure was found to possess pronounced activity against both parasites with IC50 values of 0.12 and 0.045 microM, respectively, although it was less active than the standard drug pentamidine. Compounds 2, 3, and 4 also exhibited activity against the parasites, although to a lesser extent. The activities of the compounds were further assessed by comparison with the cytotoxic activities obtained against KB cell lines.
Three new fully dehydrogenated naphthylisoquinoline alkaloids, the 7,1'-coupled ent-dioncophylleine A (3a), the likewise 7,1'-coupled 5'-O-demethyl-ent-dioncophylleine A (4), and the 7,8'-linked dioncophylleine D (5), have been isolated from the leaves of the recently described Malaysian highland liana Ancistrocladusbenomensis. All of them lack an oxygen function at C-6; this so-called Dioncophyllaceae-type structural subclass had previously been found only in naphthylisoquinoline alkaloids from West and Central African plants. Moreover, compounds 3a and 4 are the first fully dehydrogenated, i.e., only axially chiral, naphthylisoquinoline alkaloids of this type that are optically active; compound 5, by contrast, is fully racemic, due to its configurationally unstable biaryl axis. The structural elucidation was achieved by spectroscopic and chiroptical methods. Biological activities of these alkaloids against different protozoan parasites are described.
Trypanosoma evansi, the causative agent of "surra", infects many species of wild and domestic animals worldwide. In the current study, the aqueous and ethanolic extracts of six medicinal plants, namely, Aquilaria malaccensis, Derris elliptica, Garcinia hombroniana, Goniothalamus umbrosus, Nigella sativa, and Strobilanthes crispus were screened in vitro for activity against T. evansi. The cytotoxic activity of the extracts was evaluated on green monkey kidney (Vero) cells using MTT-cell proliferation assay. The median inhibitory concentrations (IC50) of the extracts ranged between 2.30 and 800.97 μg/ml and the median cytotoxic concentrations (CC50) ranged between 29.10 μg/ml and 14.53 mg/ml. The aqueous extract of G. hombroniana exhibited the highest selectivity index (SI) value of 616.36, followed by A. malaccensis aqueous extract (47.38). Phytochemical screening of the G. hombroniana aqueous extract revealed the presence of flavonoids, phenols, tannins, and saponins. It is demonstrated here that the aqueous extract of G. hombroniana has potential antitrypanosomal activity with a high SI, and may be considered as a potential source for the development of new antitrypanosomal compounds.
In our ongoing work searching for new trypanocidal lead compounds from Malaysian plants, two known piperidine alkaloids (+)-spectaline (1) and iso-6-spectaline (2) were isolated from the leaves of Senna spectabilis (sin. Cassia spectabilis). Analysis of the 1H and 13C NMR spectra showed that 1 and 2 presented analytical and spectroscopic data in full agreement with those published in the literature. All compounds were screened in vitro against Trypanosoma brucei rhodesiense in comparison to the standard drug pentamidine. Compound 1 and 2 inhibited growth of T. b. rhodesiense with an IC50 value of 0.41 ± 0.01 μM and 0.71 ± 0.01 μM, without toxic effect on L6 cells with associated a selectivity index of 134.92 and 123.74, respectively. These data show that piperidine alkaloids constitute a class of natural products that feature a broad spectrum of biological activities, and are potential templates for the development of new trypanocidal drugs. To our knowledge, the compounds are being reported for the first time to have inhibitory effects on T. b. rhodesiense. The ultrastructural alterations in the trypanosome induced by 1 and 2, leading to programmed cell death were characterized using electron microscopy. These alterations include wrinkling of the trypanosome surface, formation of autophagic vacuoles, disorganization of kinetoplast, and swelling of the mitochondria. These findings evidence a possible autophagic cell death.