ABSTRACT
A novel series of synthetic 2'-hydroxychalcones (1a-h), 2'-methoxychalcones (2a-l), flavanones (3a-k) and flavones (4a-f) have been synthesized and evaluated for their anti-inflammatory activity in carrageenan induced rat paw oedema model. Compounds 1a, 1e-g, 2e-g, 3j, and 4f showed potent anti-inflammatory activity comparable to the reference drug indomethacin with insignificant ulceration. Compound 1f showed mild inhibition against the enzymatic activity of ovine COX-1 and COX-2 (in-vitro). Compound 1f also exhibited inhibitory activity in LPS induced TNF-α production.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Chalcones/pharmacology , Cyclooxygenase Inhibitors/pharmacology , Edema/drug therapy , Flavanones/pharmacology , Flavones/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Carrageenan , Cell Line , Chalcones/chemical synthesis , Chalcones/chemistry , Cyclooxygenase 1 , Cyclooxygenase 2 , Cyclooxygenase Inhibitors/chemical synthesis , Cyclooxygenase Inhibitors/chemistry , Disease Models, Animal , Dose-Response Relationship, Drug , Edema/chemically induced , Female , Flavanones/chemical synthesis , Flavanones/chemistry , Flavones/chemical synthesis , Flavones/chemistry , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Male , Mice , Molecular Structure , Rats , Rats, Wistar , Sheep , Structure-Activity Relationship , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/biosynthesisABSTRACT
PURPOSE: Although the anti-tumor effects of carvacrol have been demonstrated earlier, the exact underlying molecular mechanisms involved in its action have not been defined and in the present study an attempt has been made to identify the mechanism of carvacrol induced cell death in human metastatic breast cancer cells, MDA-MB 231. METHODS: Apoptosis induced by carvacrol was determined based on different assays like MTT assay, Annexin V, mitochondrial membrane potential assay, multicaspase activation assay and cell cycle analysis by flow cytometer. Cleavage of PARP, cytochrome c release and modulation of Bax and Bcl2 ratio by Western blot analysis were also studied. RESULTS: The study clearly showed induction of apoptosis by carvacrol in MDA-MB 231 cells dose dependently at an IC(50) of 100 microM with a decrease in the mitochondrial membrane potential of the cells resulting in release of cytochrome c from mitochondria, caspase activation and cleavage of PARP. CONCLUSION: The data in the present study clearly demonstrated anti-tumor effects of carvacrol on human metastatic breast cancer cells, MDA-MB 231, and that the compound could have a potential therapeutic significance in treating cancer.
