Importance of Protein Kinase and Its Inhibitor: A Review

Deregulation of a broad range of protein kinases has been linked to the development and growth of cancer cells. Protein kinases are intracellular enzymes that regulate cell growth and proliferation as well as the triggering and regulation of immune responses. Protein kinases are important therapeutic targets in cancer because of their critical role in signalling mechanisms that drive malignant cell characteristics. Intensive efforts in drug research have been made in this area over the last two decades. The current study delves into the catalytic domain of a protein kinase as well as information transfer from the cell’s membrane to internal targets. It also discusses the function of protein kinases in signal transduction and their cellular signalling pathways. Furthermore, it specifically outlines a systematic method to hybrid therapies to solve the issue of protein kinase resistance. The therapeutic use of nitric oxide, as well as other targets such as Phosphoinositide 3-kinases (PI3K), Protein Kinase B (Akt), serine/threonine protein kinase (mTOR), p38 mitogen-activated protein kinases (p38 MAPK), vascular endothelial growth factor receptors (VEGFR), epidermal growth factor receptors (EGFR), and anaplastic lymphoma (ALK) etc., According to the review article, selective therapy has shown high effectiveness in the treatment of advanced cancer, with protein kinase inhibitors being a main focus of the therapy. As a result, the latest review summarized that, the current state of science with the aim of identifying a novel protein kinase inhibitor that may be utilized in the treatment of advanced cancers

The Future Perspectives of Drug Repurposing and Treatment for the Drug Resistant Breast Cancer: A Review

Breast cancer is a major health concern as it is the second leading cause of death from cancer. There are several well-known risk factors that contribute to breast cancer. Despite the various treatment options available, complete cure is still difficult due to heterogenicity of BC subtypes. As a result, identifying BC subtypes is critical for determining the optimal treatment approach. Over the last several years, new drugs targeting particular therapeutic targets have resulted in significant advances in the treatment of breast cancer. Nonetheless, resistance to treatment is the “major” issue, and a significant increase in survival rates has been the main focus for researchers. The purpose of this review article is to provide a broad overview of the molecular basis of drug resistance in breast cancer, as well as a detailed assessment of current treatment options, potential new treatment methods for drug-resistant breast cancer and repurposed drugs used for treatment. The possibility of non-cancer drugs being studied for breast cancer in the future, as well as the obstacles and bottlenecks of drug repurposing, is also highlighted. Finally, we go through present problems and future prospects in drug-resistant breast cancer therapy

An Overview of Brain Tumor

Brain tumor is an abnormal growth of mass of cells in (or) around the brain. Brain tumors can be malignant (cancerous) or being non-cancerous. It is the most common malignant primary intracranial tumors of central nervous system. Brain tumor can affect brain function if they grow large enough to press on surrounding nerves, blood vessels and tissues. Only one third of tumors formed in the brain are formed as cancerous cells. Brain tumors release molecular information to the circulation. Liquid biopsies collect and analyse tumor component in the body fluid and there is an increasing interest in investigation of liquid biopsies as substitute from tumor markers. Tumor-derived biomarkers include nucleic acids, proteins and tumor-derived extracellular vesicles that accumulate in blood (or) cerebrospinal fluid. Circulating biomarkers like O-6-methylguanine DNA methyl transferase, epidermal growth factor, isocitrate dehydrogenase, circulating tumor cells, circulating cell free micro RNAs, circulating extracellular vesicles plays and important role in causing a cancer. Brain tumor can be treated by surgery, radiation therapy (or) targeted therapy. Radiation therapy is often given afterwards. As a consequence, the most recent review reviewed the present state of research with the hopes of discovering a new brain tumor inhibitor that may be used to treat advanced malignancies

Carcinogenic effects of N-nitroso-3-(substituted phenylimino)-indolin-2-one derivatives

Aim: A novel series of N-nitroso-3-(substituted phenylimino)-indolin-2-one 3a-h was synthesized and tested for carcinogenic effects. Materials and Methods: The synthesized pyrazole derivatives′ chemical structures were proved by means of their infra red (IR), proton nuclear magnetic resonance ( 1 H-NMR), and mass,and confirmed by elemental analyses. The carcinogenic activity was assessed by 3-(4,5dimethyl thiazole-2yl)-2,5-diphenyltetrazoliumbromide (MTT) cell-viability assay. Results: The results show that most of the synthesized compounds exhibit significant carcinogenic activities. Among the synthesized compounds, N-nitroso-3-(2,4-dinitrophenylimino)-indolin-2-one 3h exhibited the most potent carcinogenic activity. Conclusion: The structure-activity relationship (SAR) studies show that the nature as well as the position of the amine are important for deciding the activity profile of the indolin-2-one derivatives, which reiterates the need for further experimental investigations

Optimization of microwave-assisted extraction of bioactive polyphenolic compounds from Marsilea quadrifolia L. using RSM and ANFIS modelling

Extraction of bioactive compounds, rich in plant secondary metabolites as a form of polyphenolic compounds has gained utmost important in the food and pharmaceutical industries due to their antioxidant properties. Microwave-assisted extraction (MAE) was utilized for maximum extraction of bioactive polyphenolic compounds from Marsilea quadrifolia L. with consuming less toxic solvent. A central composite rotatable design (CCRD) based on response surface methodology (RSM) and adaptive neuro-fuzzy inference system (ANFIS) were followed to design and optimize the experimental parameters to get highest yield of bioactive polyphenolic compounds from M. quadrifolia L. The quantitative effects of experimental parameters such as methanol concentration (X1), microwave power (X2), irradiation temperature (X3) and irradiation time (X4) were investigated to obtain the maximum yields of total phenolic (TPC), total flavonoid contents (TFC) and antioxidant properties. The optimum conditions were observed at methanol concentration (X1= 87.5 %), microwave power (X2= 25 %), irradiation temperature (X3= 60 ºC) and irradiation time (X4= 15 min). Under these conditions, the highest yields of TPC (y1)= 693.28 mg gallic acid equivalents (GAE)/g), TFC (y2)= 84.86 mg rutin equivalents (RU)/g), % DPPHsc (y3)= 81.06 %, %ABTSsc (y4)= 71.34% and FRAP (y5)= 68.09 μg mol (Fe (II)/g) has been attained. Further, the experimental results were highly acknowledged with predicted values of RSM and ANFIS. The analysis of LC-ESI-MS spectrum confirmed 6 major bioactive compounds, namely, Betasitosterol, Tridecyliodide, 2,3,7,8 tetracholorodibenzofuaran, Chlorogenic acid, Pentachlorophenylacetate and Triacontyl hexacosanoate in the optimized extract of M. quadrifolia L. The optimized extract can be used as an alternative of synthetic antioxidants for product manufacturing in food and pharmaceutical industries

Cytotoxic Potential of Bioactive Compounds from Aspergillus flavus, an Endophytic Fungus Isolated from Cynodon dactylon, against Breast Cancer: Experimental and Computational Approach

Endophytic fungi are a diverse group of microorganisms that colonize the inter- or intracellular spaces of plants and exhibit mutual benefits. Their interactions with the host plant and other microbiomes are multidimensional and play a crucial role in the production of secondary metabolites. We screened bioactive compounds present in the extracts of Aspergillus flavus, an endophytic fungus isolated from the roots of the medicinal grass Cynodon dactylon, for its anticancer potential. An in vitro analysis of the Ethyl acetate extract from A. flavus showed significant cytostatic effects (IC50: 16.25 μg/mL) against breast cancer cells (MCF-7). A morphological analysis of the cells and a flow cytometry of the cells with annexin V/Propidium Iodide suggested that the extract induced apoptosis in the MCF-7 cells. The extract of A. flavus increased reactive oxygen species (ROS) generation and caused a loss of mitochondrial membrane potential in MCF-7 cells. To identify the metabolites that might be responsible for the anticancer effect, the extract was subjected to a gas chromatography-mass spectrometry (GC-MS) analysis. Interestingly, nine phytochemicals that induced cytotoxicity in the breast cancer cell line were found in the extract. The in silico molecular docking and molecular dynamics simulation studies revealed that two compounds, 2,4,7-trinitrofluorenone and 3α, 5 α-cyclo-ergosta-7,9(11), 22t-triene-6beta-ol exhibited significant binding affinities (−9.20, and −9.50 Kcal/mol, respectively) against Bcl-2, along with binding stability and intermolecular interactions of its ligand-Bcl-2 complexes. Overall, the study found that the endophytic A. flavus from C. dactylon contains plant-like bioactive compounds that have a promising effect in breast cancer

Aphrodisiac Performance of Bioactive Compounds from Mimosa pudica Linn.: In Silico Molecular Docking and Dynamics Simulation Approach

Plants and their derived molecules have been traditionally used to manage numerous pathological complications, including male erectile dysfunction (ED). Mimosa pudica Linn. commonly referred to as the touch-me-not plant, and its extract are important sources of new lead molecules in drug discovery research. The main goal of this study was to predict highly effective molecules from M. pudica Linn. for reaching and maintaining penile erection before and during sexual intercourse through in silico molecular docking and dynamics simulation tools. A total of 28 bioactive molecules were identified from this target plant through public repositories, and their chemical structures were drawn using Chemsketch software. Graph theoretical network principles were applied to identify the ideal target (phosphodiesterase type 5) and rebuild the network to visualize the responsible signaling genes, proteins, and enzymes. The 28 identified bioactive molecules were docked against the phosphodiesterase type 5 (PDE5) enzyme and compared with the standard PDE5 inhibitor (sildenafil). Pharmacokinetics (ADME), toxicity, and several physicochemical properties of bioactive molecules were assessed to confirm their drug-likeness property. Molecular dynamics (MD) simulation modeling was performed to investigate the stability of PDE5–ligand complexes. Four bioactive molecules (Bufadienolide (−12.30 kcal mol−1), Stigmasterol (−11.40 kcal mol−1), Isovitexin (−11.20 kcal mol−1), and Apigetrin (−11.20 kcal mol−1)) showed the top binding affinities with the PDE5 enzyme, much more powerful than the standard PDE5 inhibitor (−9.80 kcal mol−1). The four top binding bioactive molecules were further validated for a stable binding affinity with the PDE5 enzyme and conformation during the MD simulation period as compared to the apoprotein and standard PDE5 inhibitor complexes. Further, the four top binding bioactive molecules demonstrated significant drug-likeness characteristics with lower toxicity profiles. According to the findings, the four top binding molecules may be used as potent and safe PDE5 inhibitors and could potentially be used in the treatment of ED