Background: Cancers are complex multi-genetic diseases that should be tackled in multi-target drug discovery scenarios. Computational methods are of great importance to accelerate the discovery of multi-target anticancer agents. Here, we employed a ligand-based approach by combining a perturbation-theory machine learning model derived from an ensemble of multilayer perceptron networks (PTML-EL-MLP) with the Fragment-Based Topological Design (FBTD) approach to rationally design and predict triple-target inhibitors against the cancerrelated proteins named Tropomyosin Receptor Kinase A (TRKA), poly[ADP-ribose] polymerase 1 (PARP-1), and Insulin-like Growth Factor 1 Receptor (IGF1R).
Methods: We extracted the chemical and biological data from ChEMBL. We applied the Box- Jenkins approach to generate multi-label topological indices and subsequently created the PTML-EL-MLP model.
Results: Our PTML-EL-MLP model exhibited an accuracy of around 80%. The application FBTD permitted the physicochemical and structural interpretation of the PTML-EL-MLP model, thus enabling a) the chemistry-driven analysis of different molecular fragments with a positive influence on the multi-target activity and b) the use of those favorable fragments as building blocks to virtually design four new drug-like molecules. The designed molecules were predicted as triple-target inhibitors against the aforementioned cancer-related proteins.
Conclusion: Our study envisages the capabilities of combining PTML modeling with FBTD for the generation of new chemical diversity for multi-target drug discovery in oncology research and beyond.
Ethnopharmacological relevance: Due to the high prevalence of cancer, researchers for the past decades have made considerable efforts for its management and treatment. Medicinal plants have always been exploited to discover novel anticancer agents. Oman's huge biodiversity has created a rich source of traditional medicine.
Objective: The current survey has aimed to document the traditionally used medicinal plants of Oman and their therapeutic role in the treatment of cancer.
Material method: This study comprises of literature-based survey through different databases, including Google, Scopus, Google Scholar, Web of Science, Science Direct, Springer Link, BioMed Central and PubMed.
Results: The current review revealed a total of 57 plant species that belong to 35 families that are used in the treatment of cancer in Oman. Most documented plants belong to Solanaceae (6 sp.), Apocyanaceae (5 sp.) and Lamiaceae (4 sp.). The literature reveals that the residents of the area mostly use leaves (38.5%) and prepare their recipes in the form of decoction (40.3%). Moreover, herbs are the most dominant life form (43.85%). Among all forms of cancer in Oman, breast (47%), wound (26), and lung cancer (0.5%) were found dominantly. A literature study confirmed that the medicinal plants used for cancer in Oman are rich in phytochemicals such as quercetin, allicin, coumarin, alliin, kaempferol, solamargine, rutin, lupeol, ursolic acid and luteolin that have shown significant biological activities including anti-cancer potential. It reflects the efficacy of these plants to be used as a medicine in clinical trials. Among all, Boswellia sacra Flueck. is of key importance due to the presence Boswellic acid being used for the treatment of different types of cancer.
Conclusion: The residents of Oman have great knowledge about the traditional use of medicinal plants for the treatment of various diseases like cancer. The therapeutic potential and physiological efficacy of Omani medicinal plants should be further explored at a molecular level via in vivo and in vitro experiments.
Background: Diabetes Mellitus (DM) is known to have an impact on the health of the male reproductive system. It is linked to low sperm quality, increased oxidative stress, and an increased generation of reactive oxygen species in the seminal fluid. Pomegranate extract has phenolic compounds and significant protective properties against oxidative stress, male sex hormone disruptions, and sperm abnormalities.
Objective: The current study aimed to evaluate the effectiveness of Pomegranate Peel Extract Nanoparticles (PPENPs) on male fertility in diabetic rats.
Methods: DM was induced in rats by intraperitoneal injection of streptozotocin (60 mg/kg). Twenty-four rats were divided into four groups, 6 rats in each group: control, DM, DM+empty NPs (60 mg/kg, orally), and DM+PPENPs (60 mg/kg, orally).
Results: Administration of PPENPs increased the levels of insulin, FSH, LH, testosterone, catalase, glutathione reduced, and semen fructose. PPENPs also improved sperm quality, as seen by improvements in sperm morphology, motility, count, and the ability of metabolically active spermatozoa to convert blue resazurin dye to pink resorufin. However, PPENPs decreased levels of glucose, malonaldehyde, nitric oxide, and sperm abnormalities. Also, histological investigation of the PPENPs showed improvement in testis tissue architecture and increased the diameter size of seminiferous tubules and germinative layer thickness.
Conclusion: Our investigation proved that the treatment of PPENPs has a protective effect on the reproductive system of male diabetic rats, improving fertility parameters, healthy sperm profiles, and the antioxidant system.
Aim: Our goal was to investigate the use of Cyclodextrin in creating an aqueous extract of Cinnamon with a high content of its bioactive ingredients, validated by cell-based assays.
Background: Due to their safety and cost-effectiveness, natural compounds have garnered attention for cancer therapy, which often faces challenges related to drug toxicity and resistance. Cinnamon (Cinnamomum verum; also known as Ceylon Cinnamon) is a commonly used spice with a history in folk medicine for treating various ailments. However, its active ingredients suffer from poor solubility, stability, and bioavailability, which limits its use and benefits.
Objective: We prepared γCyclodextrin (γCD)-assisted aqueous extract of Cinnamon (CD-CIN) and compared its activity with the DMSO extract (DM-CIN).
Methods: The cells were exposed to CD-CIN and DM-CIN extracts under normal and stressed (oxidative, metal, and hypoxic) conditions and then analyzed for stress and cancerous phenotypes using various molecular assays.
Results: We found that CD-CIN possesses considerable anticancer activity that involves the activation of tumor suppressor proteins and DNA damage response. Low, non-toxic concentrations of DM-CIN and CD-CIN caused comparable inhibition of migration and invasion capability of cells, supported by molecular marker analyses. Furthermore, protection against oxidative, metal, and hypoxia stress, as well as induction of differentiation, was recorded in both DM-CIN and CD-CIN treated cells, as compared to the control.
Conclusion: We report CD-CIN as a new economic and easy Cinnamon-derived resource that possesses considerable anticancer and antistress activities and hence warrants further chemical, in vitro, and in vivo studies.