| dc.description.abstract | In the era of resistance to the available antimalarial drugs, the discovery of antiplasmodial compounds with novel mechanism of action is needed. In this regard, plants with documented traditional uses remain an important source for such compounds. Some members of the family Asphodelaceae especially the genera: Kniphofia, Bulbine and Aloe, are used in treatment of a wide range of ailments including malaria. In this research, four plants in the Asphodelaceae family: Kniphofia foliosa, Bulbine frutescens, Aloe dawei and Aloe lateritia subspecies graminicola were investigated for antiplasmodial principles.
A total of fourty (40) compounds were isolated from the four plant species by using a combination of chromatographic methods (column chromatography on oxalic acid impregnated silica gel, Sephadex LH-20, preparative TLC) and crystallization. Characterization of the isolated pure compounds was done using spectroscopic techniques: Nuclear Magnetic Resonance (NMR), Mass Spectrometry (MS), Ultra Violet Spectroscopy (UV), Infra Red Spectroscopy (IR) and Circular Dichroism (CD). Determination of the enantiomeric purity of the two compounds was performed on chiralcel OD-H HPLC column.
From the roots of K. foliosa, eleven compounds; a pre-anthraquinone, a monomeric anthraquinone, three dimeric anthraquinones, four phenylanthraquinones and two naphthalene derivatives were isolated and characterized. Of these, the anthraquinone-anthrone dimer, 10-methoxy-10,7'-(chrysophanol anthrone)-chrysophanol (133) and the phenylanthraquinone, knipholone cyclooxanthrone (134) are new compounds. Similarly, two new compounds: 8-hydroxy-6-methylxanthone-1-carboxylic acid (138) and 6',8-O-dimethylknipholone (150) along with seven known compounds were isolated from the roots of B. frutescens. One of the known compounds, 3,8-dihydroxy-1-methylanthraquinone-2-carboxylic acid (137) where the octaketide chain is folded in an unusual way as in aloesaponarin II, was reported for the first time from the sub-family Asphodeloideae. Investigation of the roots of A. dawei has resulted in the isolation of seven naphthoquinones and ten anthraquinones. Of these, one of the naphthoquinones, 6-hydroxy-3,5-dimethoxy-2-methyl-1,4-naphthoquinone (155) is a new natural product. Furthermore, this is the second report of the occurrence of naphthoquinones in Asphodelaceae family. From the leaves of A. lateritia subspecies graminicola nine anthraquinones, three furancarboxaldehydes, and a chromone were isolated. This is the first report of the occurence of the furancarboxaldehyde derivatives in the family Asphodelaceae.
The crude extracts and the isolated compounds were tested for in vitro antiplasmodial activity against the chloroquine-resistant (W2) and chloroquine-sensitive (D6) strains of Plasmodium falciparum and showed in vitro antiplasmodial activity with the highest activity being exhibited by the dimeric anthraquinones 10-hydroxy-10,7'-(chrysophanol anthrone)-chrysophanol (132) [IC50 0.76 μg/mL against W2 and, 1.72 against D6], 10-methoxy-10,7'-(chrysophanol anthrone)-chrysophanol (133) [IC50 1.17 μg/mL against W2 and, 4.07 against D6] and chryslandicin (13) [IC50 1.53 μg/mL against W2 and, 2.14 against D6 strains].
The isolates from the roots of A. dawei were evaluated for cytotoxicity against MDA-MB-231 (ER Negative) and MCF-7 (ER Positive) breast cancer cell lines. Two of the quinones, 5,8-dihydroxy-3-methoxy-2-methylnaphthalene-1,4-dione (94) and chrysophanol-8-methyl ether (156), showed strong cytotoxicity (IC50 1.15 and 4.85 μM, respectively) against MCF-7 breast cancer cells. The isolates from K. foliosa, B. frutescens and A. lateritia subspecies graminicola were also evaluated for cytotoxicity against human cervix carcinoma KB-3-1 cell lines, and the phenylanthraquinone, knipholone (14) demonstrated strong activity with an IC50 value of 0.43 μM. Two semi-synthetic knipholone derivatives, knipholone Mannich base (163) and knipholone-1,3-oxazine (164), were prepared and tested for antiplasmodial activity against the W2 and D6 strains of Plasmodium falciparum and cytotoxicity against human cervix carcinoma KB-3-1 cell; both showed improved in the antiplasmodial activity and lower cytotoxicity compared to the parent molecule, knipholone (14).
Overall, the four plants investigated here produced a wide variety of polyketide derivatives (mainly anthraquinones, naphthoquinones, phenylanthraquinones, xanthones and furancarboxaldehydes), some of which showed antiplasmodial and cytotoxic activities | en_US |
