Several new coumarin and chromene prototype derivatives have been synthesised and evaluated for their ERa and ERb selective activity. Coumarin prototype compounds 18 & 19 were found to be ERa selective and the most active, exhibiting potential antiproliferative activity against both ER +ve & ER Àve breast cancer cell lines. The surprise finding of the series, however, are the novel prototype III chromenes 45 & 46, with aroyl substitution at the 6 th position. Both the compounds have shown potent antiproliferative activity against both the breast cancer cell lines, promote alkaline phosphatase activity, enhance osteoblast mineralization in vitro, significantly decrease ERE-ERa dependent transactivation and induce ERb activity. This specific upregulation of ERb isoform activity of compound 45 may be responsible for the antiosteoporotic activity at picomolar concentration. In addition, both the compounds were also devoid of any estrogenic activity, which correlates to their antiestrogenic behaviour in the two breast cancer cell lines. Assessment of selectivity using specific SiRNAs for ERa and ERb revealed that most of the compounds showed ERa and ERb-mediated action, except compound 28, which showed selectivity to ERa only. Computational docking analysis of active compounds 18 and 45 was conducted to correlate the interaction with the two receptors and it was found that the docked conformations of the coumarin prototype, compound 18 at ERa and ERb active sites were more or less superimposable on each other. However, the unique orientation of the aminoalkoxy side chain of novel chromene (prototype III) compound 45 in the ERb binding cavity may be responsible for its potential biological response.
In the present study, aluminium alloy (A380) composites containing 3, 6, 9 and 12 weight percentage of fl y ash particles were fabricated by liquid metallurgy technique. Three different size ranges of fl y ash particles (50 -75 μ m, 75 -103 μ m and 103 -150 μ m) were used. The composites were evaluated for hardness, tensile strength, density, dry sliding wear and frictional behaviour. Pin-on disc apparatus was used to conduct wear tests at loads of 20, 30 and 40 N at a sliding speed of 3 m/s for a constant period of 10 min. Results showed that hardness, ultimate tensile strength, wear resistance and coeffi cient of friction were superior in composites reinforced with coarse fl y ash particles (103 -150 μ m) compared to composites with fi ne particles. The hardness, ultimate tensile strength and wear resistance increased, whereas the coeffi cient of friction and density decreased with the increase in weight percentage of fl y ash. Wear resistance and coeffi cient of friction decreased with increase in applied load. Scanning electron microscope investigations of worn-out samples were carried out to study the progress of wear.
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