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In our previous study Alysicarpus vaginalis (AV) has appeared as a promising target for breast cancer hence we have screened potential targets by in silico, In Vitro and In Vivo methods. A network ...

Background: Cancer is a complex disease involving genetic and epigenetic alteration that allows cells to escape normal homeostasis. Kinases play a crucial role in signaling pathways that regulate cell functions. Deregulation of kinases leads to a variety of pathological changes, activating cancer cell proliferation and metastases. The molecular mechanism of cancer is complex and the dysregulation of tyrosine kinases like Anaplastic Lymphoma Kinase (ALK), Bcr-Abl (Fusion gene found in patient with Chronic Myelogenous Leukemia (CML), JAK (Janus Activated Kinase), Src Family Kinases (SFKs), ALK (Anaplastic lymphoma Kinase), c-MET (Mesenchymal- Epithelial Transition), EGFR (Epidermal Growth Factor receptor), PDGFR (Platelet-Derived Growth Factor Receptor), RET (Rearranged during Transfection) and VEGFR (Vascular Endothelial Growth Factor Receptor) plays major role in the process of carcinogenesis. Recently, kinase inhibitors have overcome many problems of traditional cancer chemotherapy as they effectively separate out normal, non-cancer cells as well as rapidly multiplying cancer cells. Methods: Electronic databases were searched to explore the small molecule tyrosine kinases by polyphenols with the help of docking study (Glide-7.6 program interfaced with Maestro-v11.3 of Schrödinger 2017) to show the binding energies of polyphenols inhibitor with different tyrosine kinases in order to differentiate between the targets. Results: From the literature survey, it was observed that the number of polyphenols derived from natural sources alters the expression and signaling cascade of tyrosine kinase in various tumor models. Therefore, the development of polyphenols as a tyrosine kinase inhibitor against targeted proteins is regarded as an upcoming trend for chemoprevention. Conclusion: In this review, we have discussed the role of polyphenols as chemoreceptive which will help in future for the development and discovery of novel semisynthetic anticancer agents coupled with polyphenols.

The present study intended to assess the anticancer potential of Alysicarpus vaginalis ethyl acetate fraction (AVEAF) in breast cancer cell lines (MCF-7 and MDA-MB-453) and against N-methyl-N-nitrosourea (MNU) induced mammary carcinoma in Sprague-Dawley rats which resemble the human estrogen dependent breast cancer. The SRB assay showed that the maximum growth inhibition rate of AVEAF on MCF-7 cell was 27.12 at 100 µg/ml. Flow cytometry analysis observed that AVEAF induced the cell cycle arrest at the S phases and decreased in mitochondrial membrane potential on the MCF-7 cells. AVEAF elevated intracellular ROS level in the MCF-7 cells which were reversed with N-acetycysteine (2 mM) pretreatment indicating that AVEAF induced mitochondrial-mediated apoptosis via augmentation of intracellular ROS. Western blotting exhibited that AVEAF increased the expression of pro-apoptotic protein Bax while decreasing anti-apoptotic proteins Bcl-2 and Bcl-xL expression which promoted the cleavage of caspase-9, PARP1, RIPK 1, and RIPK 3. Additionally, AVEAF exerted anticancer effect on tumor-bearing rats and the tumor inhibition rate is 50%. Data of the study indicate that AVEAF exhibits In Vitro and In Vivo anticancer activities that associate with its ROS-mediated mitochondrial-mediated intrinsic pathway of apoptosis and necroptosis in MCF-7 cells and may serve as a potential against breast cancer.

Caesalpinia pulcherima (CP) is a traditional herb used for the treatment of asthma, bronchitis, cancer, anti-bacterial, anti-fungal and as abortifacient. In the present study, bioactive components and potential targets in the treatment of breast cancer validated through in silico, in vitro and in vivo approach. The results for the analysis were as among 29 components, only four components were found active for further study which proved the use of CP as a multi-target herb for betterment of clinical uses. The results found by PPI states that our network has significant interactions which include the ESR-1, ESR-2, ESRRA, MET, VEGF, FGF, PI3K, PDK-1, MAPK, PLK-1, NEK-2, and GRK. Compound-target network involves 4 active compound and 150 target genes which elucidate the mechanisms of drug action in breast cancer treatment. Furthermore, on the basis of the above results the important proteins were fetched for the docking study which helps in predicting the possible interaction between components and targets. The results of the western blotting showed that CP regulates ER and EGFR expression in MCF-7 cell. In addition to this animal experimentation showed that CP significantly improved immunohistological status in MNU induced carcinoma rats. Network pharmacology approach not only helps us to confirm the study of the chosen target but also gave an idea of compound-target network as well as pathways associated to the CP for treating the complex metabolic condition as breast cancer and they importance for experimental verification.

Novel coronavirus (SARS-CoV-2), turned out to be a global pandemic with unstoppable morbidity and mortality rate. However, till date there is no effective treatment found against SARS-CoV-2. We report on the major in-depth molecular and docking analysis by using antiretroviral (Lopinavir and ritonavir), antimalarial (Hydroxychloroquine), antibiotics (Azithromycin), and dietary supplements (Vitamin C and E) to provide new insight into drug repurposing molecular events involved in SARS-CoV-2. We constructed three drug-target-pathways-disease networks to predict the targets and drugs interactions as well as important pathways involved in SARS-CoV-2. The results suggested that by using the combination of Lopinavir, Ritonavir along with Hydroxychloroquine and Vitamin C may turned out to be the effective line of treatment for SARS-CoV-2 as it shows the involvement of PARP-1, MAPK-8, EGFR, PRKCB, PTGS-2, and BCL-2. Gene ontology biological process analysis further confirmed multiple viral infection-related processes (P

Methods: A novel series of isoxazole (S21-S30) derivatives were designed, synthesized and screened for their anticancer activity against estrogen receptor-positive MCF-7 and negative MDA-MB-435 breast cancer cell lines. The synthesized derivative has the ability to inhibit the growth of the human breast cancer cell line at low concentrations. In vivo anticancer activity was performed on virgin female sprague dawley rats. Results: The result shows that compound S23 has more selectivity and marked estrogen modulator activity than the standard tamoxifen.

By utilizing concept of molecular hybridization, involving combination of various Pharmacophore, novel substituted coumarin-chalcone hybrids was synthesized and evaluated for anti-proliferative activity against estrogen receptor-positive MCF-7 and negative MDA-MB-435 breast cancer cell lines. In-vivo study was carried out by N-methyl nitrosourea (MNU) induced mammary carcinoma in virgin female Spraque Dawly (SD) rats. The compound 5b has highest potential than standard drug Adriamycin, comparable against Tamoxifen against ER-positive MCF-7 breast cancer cell lines. Docking study was performed to study the binding orientation and affinity of synthesized compounds on the ER-α enzyme.

A facile, green approach for the synthesis of some new dibenz[1,4] - diazepine-1-one by a three component reaction of Diamine, 1,3 diketone and aromatic aldehyde using oxalic acid as catalyst in water is described. The products are formed in good yields (92–94%). Newly synthesized dibenz [1,4]-diazepine-1-one analogues were evaluated for the anxiolytic activity by the elevated plus maze method. From the activity data it is observed that compounds, 4g , 4h and 4k show promising anxiolytic activity.

The present study intended to assess the anticancer potential of

The novel series of phenylisoxazol phenoxy 2-methylpropanoic acid derivatives were synthesized and evaluated for their in vivo hypolipidemic activity by triton WR-1339-induced hyperlipidemia in rats. The newly synthesized compounds 5a and 5i showed significant decrease in the serum TCH, TG, LDL and VLDL along with an increase in serum HDL levels as compared to standard drug Fenofibrate. The treated groups also showed significant decrease in the atherogenic index, TC:HDL risk ratios compared to cholesterol-induced hyperlipidemic control group. These molecules indeed have the potential to be developed as antihypolipidemic molecules.

A novel series of substituted quinazoline derivatives were designed, synthesized and evaluated for their hypolipidemic activity in cholesterol induced hyperlipidemic rats. In vivo screening concluded that compounds A-4, C-5 and C-6 have shown potent antihyperlipidemic activity by decreasing the plasma level of triglycerides (TG), very low density lipoprotein (VLDL), low density lipoprotein (LDL), followed by increase in level of high density lipoprotein (HDL).

A novel series of aminopyrimidines containing the phenoxy isobutyric acid group as a pharmacophore was synthesized using conventional and microwave assisted methods of synthesis. The compounds were synthesized in good yields (70-89%) by the microwave-assisted one-pot protocol in much shorter reaction times. The synthesized compounds were evaluated for their hypolipidemic and hypoglycemic activity by high-fat diet-induced hyperlipidemia and hyperglycemia in male Sprague-Dawley rats. The present investigation showed significant antihyperlipidemic and antihyperglycemic activity for all compounds of the series when compared with the standard drug. Structure-activity relationship (SAR) for the series were developed by comparing total lipid profile data of synthesized compounds with fenofibrate as standard drug.

Background: Quercetin (QUE) and Rutin (RUT) have nutritive and medicinal values. On the other hand, there are no reports of scientific assessment of its hypothalamo–pituitary–adrenal (HPA) axis modulation in the treatment of prediabetes (DM). Aim: The current study was designed to investigate the modulatory effects of QUE, RUT, and escitalopram (ESC) as antidepressants on HPA axis in chronic stress-induced pre-DM in rats. Materials and Methods: The experimental protocol was of 5 weeks. Chronic unpredictable mild stress (CUMS) was used as a model of depression to induce pre-DM in rats. The treatment was started at the end of 4 th week. After 5 th week, the plasma adrenocorticotropic hormone (ACTH), serum corticosterone (CORT), fasting blood glucose (FBG), and behavioral parameters were evaluated. Results: Oral administration of QUE (50 mg/kg), RUT (50 mg/kg), and ESC (2.5 mg/kg) to stressed control alleviated HPA axis-associated parameters (ACTH and CORT) and significantly decreased the FBG. Besides this, the depressive effects induced by CUMS were significantly improved as evident from results indicating a promising antidepressant activity. Moreover, submaximal dose of QUE (25 mg/kg) and RUT (25 mg/kg) enhanced the antidepressant activity of ESC (1 mg/kg, p.o.), which suggests that they may act through the HPA axis. Conclusion: Current results suggest that chronic stress in rats causes dysregulation of the HPA axis which leads to diabetic-like condition, i.e., “pre-DM.” It is possible that QUE, RUT, and ESC may be able to suppress the HPA axis response which could be beneficial for the treatment of stressed diabetic patients. Abbreviations used: QUE: Quercetin; RUT: Rutin; HPA: Hypothalamic–Pituitary–Adrenal Axis; CUMS: Chronic unpredictable mild stress; ACTH: Adrenocorticotropic hormone; CORT: Corticosterone; FBG: Fasting Blood Glucose; ESC: Escitalopram; FST: Fasting Blood Glucose.

The present study was undertaken to evaluate in-vivo hypolipidemic activity of a novel series of 2-methyl-2-(substituted phenyl isoxazol)phenoxyacetic acid derivatives by triton induced hyperlipidemia in rats. The newly synthesized compounds 5a, 5d and 5g showed significant decrease in the serum TCH, TG, LDL and VLDL along with an increase in serum HDL levels as compared to standard drug Fenofibrate. The treated groups also showed significant decrease in the atherogenic index and increase in % protective activity compared to control group.

All products show significant antihyperlipidemic and antihyperglycemic activity compared to the standard drug.

Inhibition of Histone deacetylases (HDACs) has been emerged as important approach to reverse aberrant epigenetic changes associated with various cancerous and non-cancerous diseases. The field of histone deacetylase inhibitors (HDIs) is moving into a new phase of development. The structure of histone deacetylases is well-established and the active sites have been well identified. Various drugs targeting this enzyme are in the pipeline for the treatment of different diseases. Since first-generation HDAC inhibitors proved their clinical fruitfulness and also second generation inhibitors are rationally designed with improved specificity, experts believe that this class will emerge in the treatment of various diseases. Considering these facts present review focuses on HDACs and developments of HDIs in the treatment of various diseases.

Propanoic acid derivative (III) undergoes cyclization with thiourea (IV) using iodine in DMF to provide aminothiazole (V) in low yield.

An improved synthetic protocol for a novel series of 2-(4-(2-substituted aminothiazole-4-yl) phenoxy)-2-methyl propanoic acid derivatives has been developed using different methods of synthesis. The synthesized compounds are evaluated for their hypolipidemic and hypoglycemic activity by high fat diet induced hyperlipidemia and hyperglycemia in Sprague–Dawley rats.