Potential topoisomerases inhibitors from Aspergillus terreus using virtual screening

Cancer is appraised as one of the predominant reasons for demise worldwide. Owing to the continued resistance to the anti-topoisomerases, the worldwide challenge is the discovery of new drugs and maintenance their topoisomerase sensitivity. Therefore, the main goal of this work is to assess the potential anti-cancer effect of the ethyl acetate extracts derived from different broth media of the endophytic Aspergillus terreus AArEF2 isolated from Artemisia arboresscens L. versus HepG-2 and MCF-7 cell lines and to estimate the ability of the most potent cytotoxic extract to inhibit topoisomerase I and II enzyme activity. The findings revealed that the ethyl acetate extract afforded from the modified potato dextrose broth (MPDB) media displayed the highest cytotoxic activities with IC50 values of 7.92 and 8.53 µg/mL towards HepG-2 and MCF-7 cell lines, respectively and showed substantial inhibition towards topoisomerase I and II with IC50 values of 8.76 and 2.83 µg/mL, respectively. HPLC-ESI-HRMS analysis of such extract annotated fifteen metabolites belonging to various classes, some of which were reported for their cytotoxic activities. Regarding docking analysis, most compounds showed strong conformational energies higher than positive control drugs, particularly averantin (12) and asterredione (14), which demonstrated promising interaction abilities with Topo I and Topo II binding sites, respectively, emphasizing probable involvement of such compounds to the noteworthy cytotoxic potentials of the ethyl acetate extract of MPDB media. Also, molecular dynamics simulation has been done to confirm the docking results. These findings might point up the probable chemotherapeutic applications of Aspergillus terreus AArEF2 isolated from A. arboresscens.