Abstract

Endophytic fungi are microorganisms that infect living plant tissues internally without producing obvious symptoms of infection, existing in a symbiotic relationship with plants for a portion of their life cycle. Currently, endophytic fungi serve as alternate sources for the production of new bioactive chemicals with great efficacy. This study aimed to examine the antimigration and anti-invasion capabilities of the endophytic fungus Aspergillus aculeatus extract, isolated from Capsicum annuum L., utilizing in vitro and in silico methods. This study isolated the endophytic fungus A. aculeatus from the leaves of C. annuum L. LC–MS analysis revealed fifty-five active components within the extract. Ten compounds exhibited favorable results in the in silico assessment. Computational predictions indicate that tajixanthone methanoate (−8.80 kcal/mol) and aspernigerin (−12.95 kcal/mol) exhibited high binding affinity against MMP-2. The A. aculeatus extract demonstrated antiproliferative activity with an IC<inf>50</inf> value of 286.36 ± 122.57 μg/mL. The extract, at noncytotoxic concentrations, reduced the migration and invasion of A549 cells in a dose-dependent manner. Furthermore, A. aculeatus extract demonstrated a marked reduction in MMP-2 activity. According to these results, the compounds may serve as antimigration and anti-invasion agents by inhibiting the MMP-2 protein. The results demonstrated that A. aculeatus extract derived from C. annuum L. inhibited A549 cell migration and invasion via reducing MMP-2 activity. The findings indicated that A. aculeatus extract derived from C. annuum L. may be utilized for the treatment of lung cancer.