Bioactive acridone alkaloids and their derivatives from Citrus aurantium (Rutaceae)

Abstract

Phytochemical studies on Citrus aurantium led to the isolation and characterization of a new secotirucallane, namely 1β-hydroxy-3,4-secotirucalla-4(28)-7,24-trien-3,21-dioic acid (1), together with the previously reported compounds citracridone I (2), citruisinine II (3), citracridone II (4), 5-hydroxynoracronycine (5), citpressine II (6), citpressine I (7), buntamine (8), 8-hydroxy-6-methoxy-3-pentylisocoumarin (9), xanthyletin (10), clausarin (11), (E)-suberenol (12), transgleinadiene (13), methoxysuberenol (14), fridelin (15), lupeol (16), limonin (17), a mixture of stigmasterol and β-sitosterol (18) and β-sitosterol-3-O-β-d-glucoside (19). The structures of these compounds were determined by comprehensive spectroscopic analyses of 1D and 2D NMR and EI- and ESI-MS and comparison with the reported data. Above compounds are reported here from this species for the first time. In addition, acetylation of citracridone I (2) and citruisinine II (3) provided the hitherto not reported monoacetyl derivatives 2a and 3a, respectively. Crude extracts, isolated compounds and derivatives were submitted to bioassays. While compound 3 showed significant antioxidant activity with IC50 of 45.5 μM, comparable to the positive control BHA with 44.2 μM, compounds 2a, 4 and 5 were significantly active in the urease inhibition assay with IC50s of 28.5, 25.5 and 29.9 μM comparable to the positive control Thiourea with 21.6 μM. Moreover, moderate to weak cytotoxicity activity was recorded for all tested compound against human large cell lung cancer cell line NCI-H460 and human squamous carcinoma cell line CAL-27 with IC50 of 32.33 and 44.52 μg/mL, respectively, compared to Cisplatin and 5-Flurouracil displaying 19.00 and 17.79 μg/mL, respectively.