How To Evaluate The Inhibitory Activity Of Rubrofusarin?

Inhibitory activities of rubrofusarin and its derivatives against AChE, BChE and BACE1
In order to evaluate the anti-AD potential of the isolated rubrofusarin and its four derivatives, we evaluated their abilities to inhibit AChE, BChE and BACE1. Results are summarized in Table 1. Of the derivatives, 3 showed most potent activity against AChE with an IC50 of 15.94 ± 0.32 µM whereas 2 had least inhibitory activity (148.08 ± 2.09 µM). 4 and 5 exhibited moderate inhibition with IC50 value of 86.05 ± 2.01 and 83.52 ± 1.56 µM, respectively, compared with the positive control berberine (0.68 ± 0.01 µM). Next, we investigated the BChE inhibitory activities of rubrofusarin and its derivatives. Unfortunately, only 3 inhibited BChE with an IC50 value of 141.15 ± 1.23 µM. Finally, the isolated compounds were investigated for their activity against BACE1. Interestingly, 4 which is devoid of methoxy group at C-8 position in the main ring was most potent with an IC50 value of 14.41 ± 2.87 µM (the positive control quercetin had an IC50 value of 21.42 ± 1.04). 1 and 3 demonstrated moderate inhibition with IC50 value of 90.01 ± 2.38 and 85.66 ± 3.98 µM, respectively. However, 5 (an isomer of 3) demonstrated no significant inhibitory activity at
According to the Dixon plot (Fig. 2), it exhibited mixed type inhibition against AChE. Moreover, the Lineweaver-Burk plot revealed a Ki value of 12.83 µM. Since 4 showed significantly high inhibitory activity against BACE1, it was also subjected to an enzyme kinetic study (Fig. 3). Its Lineweaver-Burk plot revealed a Ki value of 10.01 µM. The results of the enzyme kinetic analysis of 3 and 4 against AChE and BACE1 are shown in Table 1. Since the Ki value represents the concentration needed to combine the inhibitor with the enzyme, compounds with lower Ki value were generally preferred and are more effective inhibitors against AChE and