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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 ...

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.

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.

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 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.

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.