Antioxidant and Antiproliferative Potential of Bioactive Molecules Ursolic Acid and Thujone Isolated from Memecylon edule and Elaeagnus indica and Their Inhibitory Effect on Topoisomerase II by Molecular Docking Approach

Abstract

The present study aimed to evaluate the antioxidant and antiproliferative potential of ursolic acid and thujone isolated from leaves of Elaeagnus indica and Memecylon edule and their inhibitory effect on topoisomerase II using molecular docking study. The isolated ursolic acid and thujone were examined for different types of free radicals scavenging activity, the antiproliferative potential on U-937 and HT-60 cell lines by adopting standard methods. Further, these compounds were docked with the active site of the ATPase region of topoisomerase II. The findings of the research revealed that ursolic acid harbor strong antioxidant and antiproliferative capacity with low IC₅₀ values than the thujone in all tested methods. Moreover, ursolic acid shows significant inhibition effect on topoisomerase II with a considerable docking score (-8.0312) and GLIDE energy (-51.86 kca/mol). The present outcome concludes that ursolic acid possesses significant antioxidant and antiproliferative potential, which can be used in the development of novel antioxidant and antiproliferative agents in the future.

Figure 1

Antiproliferative potential (a and b) of isolated thujone (1-normal cells, 2-cell shrinkage, 3-membrane blebbing, 4-echinoid spikes, and 5-anoikis). (a) Antiproliferative effect of isolated thujone on U-937 cell line. (b) Antiproliferative effect of isolated ursolic acid on HL-60 cell line.

Figure 2

Antiproliferative potential (a and b) of isolated ursolic acid (1-normal cells, 2-cell shrinkage, 3-membrane blebbing, and 4-echinoid spikes). (a) Antiproliferative effect of isolated ursolic acid on U-937 cell line. (b) Antiproliferative effect of isolated ursolic acid on HL-60 cell line.

Figure 3

Binding of thujone at the interface of topoisomerase II (chain A) and the corresponding interactions with the residues.

Figure 4

Binding of thujone at the interface of topoisomerase II (double chain) and the corresponding interactions with the residues.

Figure 5

The interactions exhibited by ursolic acid with the active residues of topoisomerase II (chain A) and the corresponding interactions with the residues.

Figure 6

The binding of ursolic acid at the interface of topoisomerase II (double chain) and the corresponding interactions with the residues.