Urease and α- Chymotrypsin Inhibitory Activities and Molecular Docking Studies of Alkaloids Isolated from Medicinal Plant Isatis minima Bunge

Abstract

Phytochemical studies on the alkaloids fraction of the entire plant of Isatis minima Bunge resulted in the alkaloids 1-4 isolation, which were first time isolated from this species. The 1D and 2D NMR spectroscopic data were used to identify their structures, and there was satisfactory compatibility of the data compared to those which were previously published. In the examined compounds 1-4, Isaindigotidione (3) and Isaindigotone (4) were shown as an effective urease inhibitor in such a concentration-dependent way against Jack bean and Bacillus pasteurii urease, with IC₅₀ values 29.03 ± 0.04, 20.04 ± 0.09 and 34.03 ± 0.07, 26.13 ± 0.08 μM, respectively. Compounds 3 and 4 were likewise shown to be an effective inhibitor against α-chymotrypsin, exhibiting IC₅₀ values 16.09 ± 0.07 and 22.01 ± 0.06 μM, correspondingly. The program MOE-Dock was used to perform a molecular docking analysis to confirm probable binding modes of the active complexes of the isolated compounds 1-4 and the crystal structure of urease and α-chymotrypsin enzymes. Compound 3 was the most active, having the highest docking scores against Bacillus pasteurii urease, α-chymotrypsin, and Jack bean (-8.6876), (-7.6647), and (-13.1927) μM, respectively. All four alkaloids (1-4) showed significant urease and protease inhibitory potential and further these activities were confirmed with the help of molecular docking study.

Figure 1

Structure of compounds 1–4.

Figure 2

Docking orientation of compound 3 with the Jack bean urease enzyme active site.

Figure 3

Docking orientation of compound 3 with the Bacillus pasteurii urease enzyme active site.

Figure 4

Docking orientation of compound 3 on active site of α-chymotrypsin.

Figure 5

Activity of docking and IC₅₀ values graph prediction for (a) Jack bean urease, (b) Bacillus pasteurii urease enzyme, and (c) α-chymotrypsin enzyme.