In vitro antiproliferative, anti-inflammatory effects and molecular docking studies of natural compounds isolated from Sarcocephalus pobeguinii (Hua ex Pobég).

Background: Sarcocephalus pobeguinii (Hua ex Pobég) is used in folk medicine to treat oxidative-stress related diseases, thereby warranting the investigation of its anticancer and anti-inflammatory properties. In our previous study, the leaf extract of S. pobeguinii induced significant cytotoxic effect against several cancerous cells with high selectivity indexes towards non-cancerous cells. Aim: The current study aims to isolate natural compounds from S. pobeguinii, and to evaluate their cytotoxicity, selectivity and anti-inflammatory effects as well as searching for potential target proteins of bioactive compounds. Methods: Natural compounds were isolated from leaf, fruit and bark extracts of S. pobeguinii and their chemical structures were elucidated using appropriate spectroscopic methods. The antiproliferative effect of isolated compounds was determined on four human cancerous cells (MCF-7, HepG2, Caco-2 and A549 cells) and non-cancerous Vero cells. Additionally, the anti-inflammatory activity of these compounds was determined by evaluating the nitric oxide (NO) production inhibitory potential and the 15-lipoxygenase (15-LOX) inhibitory activity. Furthermore, molecular docking studies were carried out on six putative target proteins found in common signaling pathways of inflammation and cancer. Results: Hederagenin (2), quinovic acid 3-O-[α-D-quinovopyranoside] (6) and quinovic acid 3-O-[ß-D-quinovopyranoside] (9) exhibited significant cytotoxic effect against all cancerous cells, and they induced apoptosis in MCF-7 cells by increasing caspase-3/-7 activity. (6) showed the highest efficacy against all cancerous cells with poor selectivity (except for A549 cells) towards non-cancerous Vero cells; while (2) showed the highest selectivity warranting its potential safety as a chemotherapeutic agent. Moreover, (6) and (9) significantly inhibited NO production in LPS-stimulated RAW 264.7 cells which could mainly be attributed to their high cytotoxic effect. Besides, the mixture nauclealatifoline G and naucleofficine D (1), hederagenin (2) and chletric acid (3) were active against 15-LOX as compared to quercetin. Docking results showed that JAK2 and COX-2, with the highest binding scores, are the potential molecular targets involved in the antiproliferative and anti-inflammatory effects of bioactive compounds. Conclusion: Overall, hederagenin (2), which selectively killed cancer cells with additional anti-inflammatory effect, is the most prominent lead compound which may be further investigated as a drug candidate to tackle cancer progression.

Urease inhibitory isoflavonoids from different parts of Calopogonium mucunoides (Fabaceae).

The dichloromethane-methanol (1:1) soluble part of Calopogonium mucunoides (Fabaceae) resulted in the isolation of 10 isoflavones (4'-O-methylalpinumisoflavone, 4'-O-methylderrone, alpinumisoflavone, daidzeine, Calopogonium isoflavone A, atalantoflavone, 2',4',5',7-tetramethoxyisoflavone, 7-O-methylcuneantin, cabreuvin and 7-O-methylpseudobaptigenin) and a rotenoid (6a,12a-dehydroxydegueline). Among these, daidzeine, 7-O-methylcuneantin, atalantoflavone and 6a, 12a-dehydroxydegueline have been isolated for the first time from C. mucunoides while remaining are already reported from this source. Structures of all the isolated constituents were elucidated with the aid of NMR spectroscopic and mass spectrometric techniques. Among all the isolated constituents, nine were evaluated for their urease inhibitory potential. However, six were found potent. These include 4'-O-methylderrone, daidzeine, atalantoflavone, 2',4',5',7-tetramethoxyisoflavone, 7-O-methylcuneantin and 6a, 12a-dehydroxydegueline.

Diterpenoids from Turraeanthus mannii.

Three new compounds, 15-acetoxy-12-hydroxy-16-methyl-labda-8(17),13E-diene (1), ent-labda-8(17),13-dien-15,16-olid-19-oic acid methyl ester (2), and 12-hydroxy-labda-8(17),13-dien-15,16-olide (3), together with two known compounds, 19-acetoxy-ent-labda-8(17),13-dien-15,16-olide (4), and 16-acetoxy-12,15-epoxy-15beta-hydroxy-labda-8(17),13(16)-diene (5) were isolated from the stem bark of Turraeanthus mannii (Meliaceae). The structures of compounds 1 - 3 were elucidated by analysis of the spectroscopic data. The crude methanol extract and compound 5 exhibited weak antibacterial and antifungal activity.

Alkaloids from the stem bark of Turraeanthus africanus (Meliaceae).

Fractionation of the methanol extract of the stem bark of Turraeanthus africanus led to the isolation of two new alkaloids designated turraeanthin A and B, together with two known alkaloids. The structures of the new alkaloids were elucidated by means of spectroscopic analysis and characterized as 10-O-demethyl-17-O-methyl isoarnottianamide and 11-demethoxyl-12-methoxyl oxynitidine respectively.