Cytotoxic compounds isolated from <i>Crinum abyssinicum</i> bulbs: a combined experimental and computational study

Abstract

Abstract Crinum abyssinicum Hochst. Ex A. Rich, a plant native to Ethiopia, is traditionally used to treat various ailments, including snakebite, earache and neck cancer. Despite reports of biological studies on the plant extracts, there is no significant work reported on the phytochemical constituents of this plant species. A comprehensive phytochemical investigation of C. abyssinicum bulb led to the successful characterization of 10 known compounds; namely, flavans: (−)-(2S)-4′-hydroxy-7-methoxyflavan (1), (−)-(2S)-7, 4′-dihydroxyflavan (2); flavanone: (−)-(S)-7, 4′-dihydroxyflavanone (3); dihydrochalcone: 4-hydroxy-2,4′-dimethoxydihydrochalcone (4); alkylamides: N-E-feruloyltyramine (5), trans-N-coumaroyltyramine (6); alkaloids: hippadine (7), pratorimine (8), (+)-(3R, 4aR, 10bR, 11S)-haemanthamine (9); steroid: stigmasterol (10) reported for the first time from this species. Cytotoxicity of the isolates against MCF-7 breast cancer cell lines was carried out using the 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay method. Among the tested compounds, 1, 9 and 10 demonstrated better cytotoxic activity with half-maximal inhibitory concentration (IC50) values of 15.13, 3.17 and 1.76 µg ml−1, respectively, outperforming the standard anti-cancer drug cisplatin (IC50 = 28.37 µg ml−1). In addition, molecular docking and absorption, distribution, metabolism and excretion (ADME) studies were conducted to gain deeper insights into the interactions between the compounds and the oestrogen receptor alpha. Compounds 1, 9 and 10 showed binding energies of −7.72, −7.33 and −8.23 kcal mol−1, respectively.