Cytotoxicity of seputhecarpan D, thonningiol and 12 other phytochemicals from African flora towards human carcinoma cells.

BACKGROUND: Despite the remarkable progress in cancer therapy in recent years, this disease still remains a serious public health concern. The use of natural products has been and continues to be one of the most effective ways to fight malignancies. The cytotoxicity of 14 compounds from African medicinal plants was evaluated in four human carcinoma cell lines and normal fibroblasts. The tested samples included: ß-spinasterol (1), friedelanone (2), 16ß-hydroxylupeol (3), ß-amyrin acetate (4), lupeol acetate (5), sequoyitol (6), rhamnitrin (7), europetin 3-O-rhamnoside (8), thonningiol (9), glyasperin F (10), seputhecarpan B (11), seputhecarpan C (12), seputhecarpan D (13) and rheediaxanthone A (14). METHODS: The neutral red uptake (NR) assay was used to evaluate the cytotoxicity of samples; caspase-Glo assay, flow cytometry for cell cycle analysis and mitochondrial membrane potential (MMP) as well as spectrophotometry to measure levels of reactive oxygen species (ROS) were performed to detect the mode of action of compounds 9 and 13 in MCF-7 breast adenocarcinoma cells. RESULTS: Compounds 3, 9-13 displayed cytotoxic effects against the four tested cancer cell lines with IC50 values below 85 µM. Compounds 9 and 13 had IC50 values below 10 µM in 4/4 and 3/4 tested cell lines respectively. The IC50 values varied from 0.36 µM (against MCF7 cells) to 5.65 µM (towards colon carcinoma DLD-1 cells) for 9, from 9.78 µM (against MCF7 cells) to 67.68 µM (against HepG2 cells) for 13 and 0.18 µM (towards HepG2 cells) to 72 µM (towards Caco-2 cells) for the reference drug, doxorubicin. Compounds 9 and 13 induced cell cycle arrest in Go/G1 whilst doxorubicin induced arrest in G2/M. The two molecules (9 and 13) also induced apoptosis in MCF-7 cells through activation of caspases 3/7 and 9 as well as enhanced ROS production. CONCLUSION: Compounds 9 and 13 are good cytotoxic phytochemicals that should be explored more in future to develop a cytotoxic drug to fight human carcinoma.

Two new pterocarpans and a new pyrone derivative with cytotoxic activities from Ptycholobium contortum (N.E.Br.) Brummitt (Leguminosae): revised NMR assignment of mundulea lactone.

BACKGROUND: Ptycholobium is a genus related to Tephrosia which comprises only three species. Compared to Tephrosia, which has been phytochemically and pharmacologically studied, Ptycholobium species have only few or no reports on their chemical constituents. Moreover, no studies on the cytotoxic activities of its secondary metabolites have been previously documented. RESULTS: From the non polar fractions of the roots bark of Ptycholobium contortum (syn Tephrosia contorta), two new pterocarpans: seputhecarpan C 1 and seputhecarpan D 2 and a new pyrone derivative, ptycholopyrone A 3 were isolated. Alongside, five known compounds identified as 3-α,α-dimethylallyl-4-methoxy-6-styryl-α-pyrone or mundulea lactone 4, glyasperin F 5, seputhecarpan A 6, seputheisoflavone 7 and 5-O-methyl-myo-inositol or sequoyitol 8 were also obtained. Their structures were established by the mean means of spectroscopic data in conjunction to those reported in literature. The NMR assignment of the major compound mundulea lactone 4 is revised in this paper. In addition, the cytotoxicity of the isolated metabolites was evaluated on two lung cancer cell lines A549 and SPC212. 8 was not active while compounds 1, 2, 4-7 displayed antiproliferative effects against the two carcinoma cell lines with IC50 values below 75 µM. IC50 values below 10 µM were obtained for 4, 6 and 7 on SPC212 cells. CONCLUSION: Based on the obtained results, Ptycholobium contortum turns to be a rich source of phenolic metabolites among them some bearing prenyl moieties. This study reports for the first time the isolation of pyrone derivatives 3 and 4 from Ptycholobium genus. The cytotoxicity observed for the isolate is also reported for the first time and shows that 4, 6 and 7 could be chemically explored in order to develop a hit candidate against lung cancer. Graphical abstractTwo new pterocarpans and a new pyrone derivative with cytotoxic activities from ptycholobium contortum (N.E.Br.) Brummitt (Leguminosae): revised NMR assignment of mundulea lactone.