In silico and in vitro anti-inflammatory evaluation of 2,6-bis-(3'-ethoxy, 4'-hydroxybenzylidene)-cyclohexanone, 2,6-bis-(3'-Bromo,4'-methoxybenzylidene)-cyclohexanone, and 2,6-bis- (3',4'-dimethoxybenzylidene)-cyclohexanone

The aim of this research is to design the new mono-carbonyl analogs of curcumin, synthesize the molecules, anddetermine its activity in cyclooxygenase inhibition in vitro and in silico. New design MACs were performed bythe Quantitative Structure–Activity Relationship (QSAR) study using the BuildQSAR program. 2,6-bis-(3ʹ-ethoxy,4ʹ-hydroxybenzylidene)-cyclohexanone, 2,6-bis-(3ʹ-Bromo, 4ʹ-methoxybenzylidene)-cyclohexanone, and 2,6-bis-(3ʹ,4ʹ-dimethoxybenzylidene)-cyclohexanone had been synthesized using aldol condensation reaction. The anti-inflammatoryassay was performed to measure the level of malondialdehyde. In silico studies were carried out to evaluate the activityof cyclooxygenase inhibition in cyclooxygenase-1 and cyclooxygenase-2 specific proteins. Molecular operatingenvironment program was used for protocol docking. The results of the QSAR study reveal the good relationshipof anti-inflammatory activities. The in vitro anti-inflammatory activities of 6-bis-(3ʹ-ethoxy, 4ʹ-hydroxybenzylidene)-cyclohexanone, 2,6-bis-(3ʹ-Bromo, 4ʹ-methoxybenzylidene)-cyclohexanone, and 2,6-bis-(3ʹ,4ʹ-dimethoxybenzylidene)-cyclohexanone indicate the promising potential to inhibit cyclooxygenase enzyme with IC50 13.53 μM, 11.56 μM,and 20.52 μM, respectively. The in silico evaluation showing that O atoms (47, from ketones) of 2,6-bis-(3ʹ-Bromo,4ʹ-methoxybenzylidene)-cyclohexanone interact with ARG120 and TYR355 through H acceptor.

Combination of low-concentration of novel phytoestrogen (8,9)-furanyl-pterocarpan-3-ol from Pachyrhizus erosus attenuated tamoxifen-associated growth inhibition on breast cancer T47D cells

Objective: To investigate the estrogenic effect of (8,9)-furanyl-pterocarpan-3-ol (FPC) on growth of human breast cancer T47D cells and the interactions between the FPC and tamoxifen (TAM), on the growth of estrogen receptor-dependent breast cancer T47D cells.Methods:T47D cells were treated with FPC alone (0.01-200 μmol/L) or in combination with TAM 20 nmol/L. The proliferation effect of FPC were conducted on T47D cells in vitro by MTT test. Furthermore, the expression of ERα or c-Myc were also determined by immunohistochemistry.Results:inhibitory effect on T47D cells, wheraes co-administered with low concentration (less than 1μmol/L) of FPC attenuated to promote cell proliferation. In contrast, the combination of TAM with higher doses (more than 20 μmol/L) of FPC showed growth inhibitory. This result was supported by immunocytochemistry studies that the administration of 20 nmol/L TAM down-regulated ER-αand c-Myc, but the combination of 20 nmol/L TAM and 1 μmol/L FPC robustly up-regulated expression of ER-α. Thus, the reduced growth inhibition of TAM 20 nmol/L by FPC 1 μmol/L on T47D cells may act via the modulation of ER-α.Conclusions:The findings indicate and suggest that FPC had estrogenic activity at low The results indicated that administration of an anti-estrogen TAM showed growth concentrations and anti-estrogenic effect that are likely to be regulated by c-Myc and estrogen receptors. We also confirm that low concentration of FPC attenuated the growth-inhibitory effects of TAM on mammary tumor prevention. Therefore, the present study suggests that caution is warranted regarding the consumption of dietary FPC by breast cancer patients while on TMA therapy.