A 3D-QSAR Model of the Tyrosinase Inhibitory Activity of Curcumin Analogues
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Abstract:
As a rational drug design approach, the three-dimensional quantitative structure-activity relationship (3D-QSAR) is one of the methods that is currently used most often for drug design and development. Based on the relationship between the structure and tyrosinase inhibitory activity of 28 curcumin analogues, a 3D-QSAR model with statistical significance was established, with a cross-validation correlation coefficient q2 of 0.609, a correlation coefficient R2 of 0.997, and an F statistic of 77.070. The reliability and predictive ability of the model were analyzed. Six curcumin analogues (A1, A2, B1, B2, B3, and B4) with a symmetrical structure were designed based on the model. These compounds were then synthesized, separated, and purified, and their structures were characterized. Among them, compounds A2 and B3 were new compounds that have not previously been reported. Using levodopa (L-DOPA) as substrate, the tyrosinase inhibitory activities of the six compounds were measured. Among them, B1 exhibited the strongest activity, and the activities of all compounds were higher than that of curcumin. Additionally, the experimental values were very close to the predicted values, suggesting that the 3D-QSAR model has good external predictive capabilities.
