Chemopreventive Agents from Nature: A Review of Apigenin, Rosmarinic Acid, and Thymoquinone.

Cancer, a major challenge to global health and healthcare systems, requires the study of alternative and supportive treatments due to the limitations of conventional therapies. This review examines the chemopreventive potential of three natural compounds: rosmarinic acid, apigenin, and thymoquinone. Derived from various plants, these compounds have demonstrated promising chemopreventive properties in in vitro, in vivo, and in silico studies. Specifically, they have been shown to inhibit cancer cell growth, induce apoptosis, and modulate key signaling pathways involved in cancer progression. The aim of this review is to provide a comprehensive overview of the current research on these phytochemicals, elucidating their mechanisms of action, therapeutic efficacy, and potential as adjuncts to traditional cancer therapies. This information serves as a valuable resource for researchers and healthcare providers interested in expanding their knowledge within the field of alternative cancer therapies.

Multi-Epitope Vaccine Design against Monkeypox Virus via Reverse Vaccinology Method Exploiting Immunoinformatic and Bioinformatic Approaches.

(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.

Role of vitamin D in targeting cancer and cancer stem cell populations and its therapeutic implications.

Cancer is recognized globally as the second-most dominating and leading cause of morbidities. Fighting the global health epidemic threat posed by cancer requires progress and improvements in imaging techniques, surgical techniques, radiotherapy, and chemotherapy. The existence of a small subpopulation of undifferentiated cells known as cancer stem cells has been supported by accumulating evidence and ongoing research. According to clinical data, cancer recurrence, tumor development, and metastasis are thought to be caused by CSCs. Nutritional or dietary supplements can help you to fight against cancer and cope with the treatment side effects. Vitamin D, sometimes known as the sunshine vitamin, is produced in the skin in reaction to sunlight. Vitamin D deficiency is hazardous to any degree, increasing the risk of diseases such as cancer and disorders like osteoporosis. Bioactive vitamin D, or calcitriol, regulates several biological pathways. Many modes of action of Vitamin D might be helpful in protecting somatic stem cells (e.g., DNA damage repair and oxidative stress protection) or restricting cancer stem cell growth (e.g., cell cycle arrest, cell apoptosis). Researchers have recently begun to investigate the inhibitory effects of dietary vitamin D on cancer stem cells. In this review, we investigated the therapeutic impact of vitamin D and its molecular processes to target cancer and cancer stem cells as well.

Structure-Based Discovery and Bioactivity Evaluation of Novel Aurora-A Kinase Inhibitors as Anticancer Agents via Docking-Based Comparative Intermolecular Contacts Analysis (dbCICA).

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.

Plant-Derived Natural Products in Cancer Research: Extraction, Mechanism of Action, and Drug Formulation.

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.

Discovery of novel Flt3 inhibitory chemotypes through extensive ligand-based and new structure-based pharmacophore modelling methods.

Flt3 is an oncogenic kinase involved in different types of leukemia. It is most prominently associated with acute myeloid leukemia (AML). Flt3-specific inhibitors have shown promising results in interfering with AML prompting us to model this interesting target. We implemented ligand-based, QSAR-guided, pharmacophore exploration combined with novel structure-based computational workflow based on docking-based comparative intermolecular contacts analysis (db-CICA) combined with homology modelling to explore the pharmacophoric features of 93 diverse cyclic Flt3 inhibitors. The resulting pharmacophore models were used as virtual search queries to scan the National Cancer Institute (NCI) database for novel Flt3 inhibitory leads. Ten hits of novel scaffolds were captured showing anti-Flt3 IC50 values ranging from 1.2 to 14.7 µM. Interestingly, six of them illustrated low micromolar and submicromolar potencies against the mutated active form of Flt3 (Flt3D835Y) and the related vascular endothelial growth factor receptor 2 (VEGFR2).