UHPLC/GC-qTOF-MS metabolomics, MTT assay, and molecular docking studies reveal physostigmine as a new anticancer agent from the ethyl acetate and butanol fractions of Kigelia africana (Lam.) Benth. fruit extracts

Kigelia africana plant is widely used as an herbal remedy in preventing the onset and the treatment of cancer-related infections. With the surge in the research interest of the plant, the specific chemical compound or metabolite that confer its anticancer properties has not been adequately investigated. The ethyl acetate and butanol fractions of the fruit extracts were evaluated by 2-(4,5-dimethylthiazol-2-yl)-3,5-diphenyl-2H-tetrazolium bromide (MTT) assay against four different cell lines with the ethyl acetate fraction having IC₅₀ values of 0.53 and 0.42 μM against Hep G2 and HeLa cells respectively. More than 235 phytoconstituents were profiled by UHPLC-qTOF-MS/MS while more than 15 chemical compounds were identified by GC-MS from the fractions. Molecular docking studies revealed that physostigmine, fluazifop, dexamethasone, sulfisomidine, and desmethylmirtazapine could favorably bind at higher binding energies of -8.3, -8.6, -8.2, and -8.1 kcal/mol respectively better than camptothecin with binding energy of -7.9 kcal/mol. The results of this study showed that physostigmine had better interactions with topoisomerase IIα and a high score of pharmacokinetic prediction using ADMET profiles thereby suggesting that drug design using physostigmine as a base structure could serve as an alternative against the toxic side effects of doxorubicin and camptothecin.

Keywords: GC-MS; Kigelia africana; UHPLC-qTOF-MS/MS; camptothecin; doxorubicin; physostigmine.