Cytotoxicity, Antimicrobial Activity, Molecular Docking, Drug likeness and DFT Analysis of Benzo[c]phenanthridine Alkaloids from Roots of Zanthoxylum chalybeum

Zanthoxylum chalybeum (Rutaceae) is traditionally used to treat malaria, tuberculosis, intestinal problems and pneumonia. Roots extract was subjected to silica gel column chromatographic separation to afford four benzo[c]phenanthridines alkaloids (1-4), of which compounds (2) and (3) are reported herein for the first time from the species. Cytotoxicity analysis revealed chelerythrine (1) and dihydrochelerythrine (4) induced a significant reduction of cell growth of MDA-MB-231 and MCF-7 breast cancer cell lines in a dose-dependent manner. Chelerythrine (1) showed the highest potency against the aggressive and metastatic MDA-MB-231 cell line (IC50 = 3.616 ± 0.51 µM). The compounds showed the influence in the cell cycle in the MDA-MB-231 cell line by arresting some cells in the G2/M phase, preventing cells with damaged DNA from entering mitosis. Chelerythrine (1) showed promising antibacterial and antifungal activity against S. aureus and C. albicans with IC50 = 12.5 µg/mL and IC50 = 50 µg/mL, respectively. Molecular docking analysis of alkaloids (1-4) revealed lowest binding energy ranged from -6.5 to -7.5 and -6.1 to -6.4 Kcal/mol targeting E.coli DNA gyrase B and topoisomerase II α, respectively. The results obtained from molecular docking, drug-likeness properties, ADMET and DFT analysis agree with those obtained from experimental studies. Hence, chelerythrine (1) and dihydrochelerythrine (4) have proved to have promising activity against infectious diseases caused by microorganisms and human breast cancer cells, suggesting the potential use of the compounds as medicine which corroborate the traditional uses of the plant.