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.
Aim: We aimed to investigate the potential inhibitory effects of diterpenes on SARS-CoV-2 main protease (Mpro). Materials & methods: We performed a virtual screening of diterpenoids against Mpro using molecular docking, molecular dynamics simulation and absorption, distribution, metabolism and excretion) analysis. Results: Some tested compounds followed Lipinski’s rule and showed drug-like properties. Some diterpenoids possessed remarkable binding affinities with SARS-CoV-2 Mpro and drug-like pharmacokinetic properties. Three derivatives exhibited structural deviations lower than 1 Å. Conclusion: The findings of the study suggest that some of the diterpenes could be candidates as potential inhibitors for Mpro of SARS-CoV-2.
Toll-like receptors (TLRs) control both innate and adaptive immunity with a wide expression on renal epithelial cells and leukocytes. Activation of TLRs results in the production of cytokines, chemokines and interferons along with activation of the transcription factor NF-κB, resulting in inflammatory perturbations. TLR4 signaling pathway is the most extensively studied of TLRs. TLR4 is expressed on renal microvascular endothelial and tubular epithelial cells. So, targeting TLR4 modulation could be a therapeutic approach to attenuate kidney diseases that are underlined by inflammatory cascade. Medicinal plants with anti-inflammatory activities display valuable effects and are employed as alternative sources to alleviate renal disease linked with inflammation. Flavonoids and other phytochemicals derived from traditional medicines possess promising pharmacological activities owing to their relatively cheap and high safety profile. Our review focuses on the potent anti-inflammatory activities of twenty phytochemicals to verify if their potential promising renoprotective effects are related to suppression of TLR4 signaling in different renal diseases, including sepsis-induced acute kidney injury, renal fibrosis, chemotherapy-induced nephrotoxicity, diabetic nephropathy and renal ischemia/reperfusion injury. Additionally, molecular docking simulations were employed to explore the potential binding affinity of these phytochemicals to TLR4 as a strategy to attenuate renal diseases associated with activated TLR4 signaling.
The endophytic fungus Paecilomyces sp. (AUMC 15510) was isolated from healthy stem samples of the Egyptian medicinal plant Cornulaca monacantha. We used GC–MS and HPLC analysis to identify the bioactive constituents of ethyl acetate crude extract of Paecilomyces sp. (PsEAE). Six human microbial pathogens have been selected to evaluate the antimicrobial activity of PsEAE. Our data showed that the extract has significant antimicrobial activity against all tested pathogens. However, the best inhibitory effect was observed against Bacillus subtilis ATCC 6633 and Pseudomonas aeruginosa ATCC 90274 with a minimum inhibitory concentration (MIC) of 3.9 μg/ml and minimum bactericidal concentration (MBC) of 15.6 μg/ml, for both pathogens. Also, PsEAE exerts a significant inhibition on the biofilm formation of the previously mentioned pathogenic strains. In addition, we evaluated the wound healing efficiency of PsEAE on earthworms (Lumbricus castaneus) as a feasible and plausible model that mimics human skin. Interestingly, PsEAE exhibited a promising wound healing activity and enhanced wound closure. In conclusion, Paecilomyces sp. (AUMC 15510) could be a sustainable source of antimicrobial agents and a potential therapeutic target for wound management.
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