Enzyme inhibitors cause a decrease in the reaction rate of an enzyme-catalyzed reaction by binding to a specific portion of an enzyme and thus slowing or preventing a reaction from occurring. Synthetic Route of 4923-87-9, C8H5BrS. A document type is Article, introducing its new discovery., Synthetic Route of 4923-87-9
A series of novel 1-substituted-2-aryl imidazoles (SAI) were designed and synthesized based on our previously reported ABI (2-Aryl-4-Benzoyl Imidazole) analogs and on the structure of combretastatin A-4 (CA-4). These compounds showed potent antiproliferative activities against six human cancer cell lines with IC50 values in nano molar range. Among them, compound 3X exhibited the best anticancer activity with an average IC50 value of ?100 nM. The compound maintains the mechanism of action by inhibiting tubulin polymerization, thus causing cell arrest at G2/M phase and apoptosis. In vivo efficacy studies indicated that 3X was highly effective in suppressing tumor growth in a MDA-MB-468 xenograft model of nude mouse with a TGI (Tumor Growth Suppression) of 77% at 60 mg/kg without causing significant toxicity. In addition, 3X displayed significantly better water solubility (36.70 mug/mL) than CA-4 (2.83 mug/mL). Molecular modeling study indicated that 3X binds well to the colchicine binding site in tubulin. Our results suggest that the novel SAI analogs deserve further investigation as potential anticancer agents.
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Reference:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem