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

Abstract

Kigelia africana plant is widely used as a herbal remedy in preventing the onset and the treatment of cancer‐related infections. With the increase in the research interest of the plant, the specific chemical compound or metabolite that confers 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 assay against four different cell lines, with the ethyl acetate fraction having inhibition concentration values of 0.53 and 0.42 μM against Hep G2 and HeLa cells, respectively. More than 235 phytoconstituents were profiled using UHPLC‐TOF‐MS, while more than 15 chemical compounds were identified using 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 a binding energy of –7.9 kcal/mol. The results of this study showed that physostigmine interacted well with topoisomerase IIα and had a high score of pharmacokinetic prediction using absorption, distribution, metabolism, excretion, and toxicity 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.

Research Progress and Trends in Metabolomics of Fruit Trees

“…Fifteen compounds were identified from the Kigelia africana fruit using UHPLC-TOF-MS and GC-MS. In which, physostigmine was demonstrated with an excellent anticancer activity (Fagbohun et al, 2021). In addition, nine antiaging compounds in Nephelium lappaceum (rambutan) seeds were identified (Lee et al, 2020).…”

The potential of 4-aryl-6-morpholino-3(2H)-pyridazinone-2-arylpiperazinylacetamide as a new scaffold for SIRT2 inhibition: in silico approach guided by pharmacophore mapping and molecular docking

“…In silico ADMET predictions revealed that except having hERG inhibition potential, the compounds 11-14 showed good predicted blood-brain, Caco, and MDCK permeability. Predicted oral absorption values were found to be high where the human serum albumin binding capacities were calculated within suitable limits [45,46].…”

First Report of Clonostachys rosea as a Mycoparasite on Sclerotinia sclerotiorum Causing Head Rot of Cabbage in India

“…After removing the eluent, the final products of the metabolites were dissolved in 1 mL of HPLC-grade methanol. The resulting mixtures were filtered with a 0.25 μm polyvinylidene difluoride membrane syringe-like filter and extracted using a sodium sulfate cartridge to remove water and then concentrated to 1 mL with a turbovap at 55 °C with nitrogen before GC-MS analysis [ 64 ].…”