GC–MS analysis, cytotoxicity, and molecular docking studies of bioactive alkaloids extracted from tomato leaves inoculated with endophytic fungus Beauveria sp. AUMC 15401

Abstract

The term endophyte refers to a group of microbes that inhabit plant internal tissues such as bacteria and fungi. In this study, we isolated Beauveria sp. AUMC 15401 from the internal tissues of tomato leaves and extracted the alkaloidal contents from the leaves. Also, gas chromatography–mass spectrometry (GC–MS) analysis was used to identify the composition of the alkaloidal extract. The analysis showed that Beauveria sp. AUMC 15401 colonization stimulates plant secondary metabolism to produce novel alkaloids compared with the control tomato extract. Furthermore, the alkaloidal extract from the infected tomato leaves showed a high cytotoxic effect against A549 adenocarcinoma human alveolar basal epithelial cells. In addition, molecular docking studies were performed to investigate the potential binding of each alkaloid in the extract with epidermal growth factor receptor, vascular endothelial growth factor receptor 2, and SRC tyrosine kinases. These proteins are the main key factors in epithelial malignancies and their inhibition could reduce tumor growth. A pharmacokinetic study (absorption, distribution, metabolism, and excretion) was also conducted to determine the potential of the isolated alkaloids to be oral active candidates. Novelty impact statement Beauveria sp. AUMC 15401 colonization in tomatoes stimulates the production of the secondary metabolite of bioactive alkaloids that exhibited promising cytotoxic activity against A549 adenocarcinoma human alveolar basal epithelial cells. Multiple approaches have been used to assess the drug-like properties of the secreted alkaloids and verify their potential inhibitory action on the proteins that regulate cell proliferation and metastasis. This study emphasized the necessity of employing sustainable bioactive compounds from nature as a potential alternative to chemical-based therapies.