ABSTRACT
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.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Isoxazoles/chemistry , Isoxazoles/therapeutic use , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Breast/drug effects , Breast/metabolism , Breast/pathology , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Design , Female , Humans , Isoxazoles/chemical synthesis , Isoxazoles/pharmacology , MCF-7 Cells , Molecular Docking Simulation , Rats, Sprague-Dawley , Receptors, Estrogen/metabolismABSTRACT
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.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Mammary Neoplasms, Experimental/drug therapy , Animals , Drug Design , Drug Evaluation, Preclinical , Female , Mammary Neoplasms, Experimental/chemically induced , Molecular Structure , Rats , Rats, Sprague-Dawley , Structure-Activity RelationshipABSTRACT
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.
