Cytotoxicity, Molecular Docking, ADMET and DFT Analysis of Alkaloids from the Roots and Fruits ofVepris dainelli

Abstract

Background: Vepris dainelli (Rutaceae) is an endemic medicinal plant to Ethiopia, traditionally used for the treatment of abdominal cramp, intestinal worms, skin diseases and tooth pain. Methods: Roots and fruit extracts were subjected to silica gel column chromatographic separation to afford five alkaloids, reported for the first time from the species. The cytotoxic effects of alkaloids (2-4) were evaluated in vitro against the estrogen-responsive MCF-7 and estrogen-unresponsive MDA-MB-231 human breast cancer cell lines by MTS assay. Result: The results revealed that alkaloids (2-4) induced a significant reduction in cell growth of both breast cancer cell lines in a dose-dependent manner. Evodiamine (4) showed the highest potency against the aggressive metastatic MDA-MB-231 cell line at low micromolar concentrations. In addition, it highly arrested the cells in the G2/M phase, especially the MCF-7 cell line. By contrast, evoxanthine (2) and arborinine (3) exhibited higher cytotoxicity against MCF-7 than MDA-MB-231, and showed influencing the cell cycle in both cell lines by arresting some cells in the G2/M phase, preventing cells with damaged DNA from entering mitosis. Molecular docking analysis showed that all alkaloids inhibit human topoisomerase II α, compared with vosaroxin anti-cancer agent under clinical trial. The ADMET studies showed the alkaloids' highest drug-likeness properties, suggesting these alkaloids act as a drug and exhibit remarkable biological activities, except (5). DFT calculations indicated that studied alkaloids showed the lowest gap energy and were chemically reactive. Conclusion: We found that the results obtained from molecular docking, drug-likeness properties, ADMET analysis and DFT calculation are in good agreement with experimental studies. Hence, evoxanthine (2), arborinine (3), and evodiamine (4) may serve as a lead molecule that could be developed into potent topoisomerase II α inhibitors against human breast cancer cells.

Solar-Assisted Green Synthesis, Molecular Docking, Antibacterial, and Cytotoxicity Studies of Symmetrical N, N’-Alkylidene Bisamides Bearing Lower E-Factors

“…[45] Most importantly, the cytotoxicity, carcer and process management also received a vital task in recent trends. [46][47][48][49] Solar radiation is considered a potential and sustainable resource of energy. Globally, solar energy is considered a plentiful renewable energy source because the user does not cause the emission of CO 2 or other harmful gases.…”

“…This assay is vastly used to determine the cytotoxicity of the drugs or compounds on cancerous cells or primary patient cells46. Here, in this study, the cytotoxicity effects of various compounds is evaluated on the highly aggressive subtype of breast cancer TNBC (Triple-Negative Breast Cancer) cell line MDAMB 231 [47,48]. Scheme 1.…”