Cancer is one of the main causes of death globally and considered as a major challenge for the public health system. The high toxicity and the lack of selectivity of conventional anticancer therapies make the search for alternative treatments a priority. In this review, we describe the main plant-derived natural products used as anticancer agents. Natural sources, extraction methods, anticancer mechanisms, clinical studies, and pharmaceutical formulation are discussed in this review. Studies covered by this review should provide a solid foundation for researchers and physicians to enhance basic and clinical research on developing alternative anticancer therapies.
(1) Background: The monkeypox virus is a zoonotic orthopox DNA virus that is closely linked to the virus. In light of the growing concern about this virus, the current research set out to use bioinformatics and immunoinformatics to develop a potential vaccine against the virus. (2) Methods: A multiepitope vaccine was constructed from the B-cell and T-cell epitopes of the MPXVgp181 strain using adjuvant and different linkers. The constructed vaccine was predicted for antigenicity, allergenicity, toxicity, and population coverage. In silico immune simulation studies were also carried out. Expression analysis and cloning of the constructed vaccine was carried out in the pET-28a(+) vector using snapgene. (3) Results: The constructed vaccine was predicted to be antigenic, non-allergenic, and non-toxic. It was predicted to have excellent global population coverage and produced satisfactory immune response. The in silico expression and cloning studies were successful in E. coli, which makes the vaccine construct suitable for mass production in the pharmaceutical industry. (4) Conclusion: The constructed vaccine is based on the B-cell and T-cell epitopes obtained from the MPXVgp181 strain. This research can be useful in developing a vaccine to combat the monkeypox virus globally after performing in-depth in vitro and in vivo studies.
Antimicrobial resistance is increasing globally and is one of the major public health concerns. This highlights the need to search for new antimicrobial agents. Natural fruit by-products are a rich source of bioactive compounds. Pomegranate (Punica granatum) fruit is particularly rich in phenolic bioactive phytochemicals. These compounds are known for their antioxidant, anti-inflammatory, and anticancer properties. Furthermore, they exhibit a broad spectrum of antimicrobial effects. Bioactive phytochemicals are found mainly in peel (exocarp and mesocarp), which constitutes about 50% of the whole fresh fruit. This study utilized pomegranate of Jordanian origin to evaluate the antimicrobial activity of different Pomegranate peel extracts (PPEs) alone and/or in combination with antibacterial agents against four bacterial strains. Different solvents and extraction methods were employed to obtain the PPEs. A key focus was to explore the enhancement of antibacterial activity against gentamicin-resistant Pseudomonas aeruginosa (P. aeruginosa) when microwaved aqueous extracts are combined with gentamicin. The antibacterial activity of PPEs varied depending on the extraction method and the solvent used. Notably, the aqueous macerate and microwave-assisted extract showed high potency and similar activity against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and P. aeruginosa (MICs 12.5, 25, and 25 μg/μL, respectively for both aqueous extracts). In contrast, Proteus mirabilis (P. mirabilis) was more susceptible to the inhibitory activity of organic PPEs with a MIC of 25 μg/μL recorded with the use of ethanolic solvents. Bacterial antagonistic activity was observed against gentamicin-resistant P. aeruginosa, particularly when lower concentrations (3.125, 1.562, 0.781, and 0.39 μg/μL) of microwaved aqueous PPEs were evaluated in combination with different concentrations of gentamicin. In conclusion, pomegranate peels, a natural and safe by-product, demonstrate promising antimicrobial potential. Furthermore, combining PPEs with conventional antibiotics shows promise in addressing antibiotic resistance, highlighting their potential role in treating infectious diseases.
1 May 2019 in Journal of Molecular Graphics and Modelling
Aurora-A kinase plays a central role in mitosis, where aberrant activation contributes to cancer by promoting cell cycle progression, genomic instability, epithelial-mesenchymal transition, and cancer stemness. Aurora-A kinase inhibitors have shown encouraging results in clinical trials but have not gained Food and Drug Administration (FDA) approval. An innovative computational workflow named Docking-based Comparative Intermolecular Contacts Analysis (dbCICA) was applied—aiming to identify novel Aurora-A kinase inhibitors—using seventy-nine reported Aurora-A kinase inhibitors to specify the best possible docking settings needed to fit into the active-site binding pocket of Aurora-A kinase crystal structure, in a process that only potent ligands contact critical binding-site spots, distinct from those occupied by less-active ligands. Optimal dbCICA models were transformed into two corresponding pharmacophores. The optimal one, in capturing active hits and discarding inactive ones, validated by receiver operating characteristic analysis, was used as a virtual in-silico search query for screening new molecules from the National Cancer Institute database. A fluorescence resonance energy transfer (FRET)-based assay was used to assess the activity of captured molecules and five promising Aurora-A kinase inhibitors were identified. The activity was next validated using a cell culture anti-proliferative assay (MTT) and revealed a most potent lead 85(NCI 14040) molecule after 72 h of incubation, scoring IC50 values of 3.5–11.0 μM against PANC1 (pancreas), PC-3 (prostate), T-47D and MDA-MB-231 (breast)cancer cells, and showing favorable safety profiles (27.5 μM IC50 on fibroblasts). Our results provide new clues for further development of Aurora-A kinase inhibitors as anticancer molecules.