In Vitro and In Silico Anticancer Evaluation of Secondary Metabolites from an Endophytic Fungus Aspergillus Fumigatus Isolated from Monarda Citriodora

Abstract

AbstractChemical investigation of endophytic fungal extract of Aspergillus fumigatus strain KF436391 isolated from medicinal plant Monarda citriodora yielded one new compound 2‐methylenedecanedioic acid (1) along with seventeen known compounds (2–18) including (E)‐Undec‐2‐enedioic acid (2), Ergosterol (3) Ditryptophenaline (4), Gliotoxin (5), Pseurotin A (6), 12, 13‐dihydroxyfumitremorgin C (7), Brevianamide F (8), Demethoxy fumitremorgin C (9), Fumitremorgin C (10), Bisdethiobis (methylthio) gliotoxin (11), Cephalimysin A (12), Neofipiperazine C (13), Antibiotic FD838 (14), Monomethylsulochrin (15), trans‐p‐coumaric acid (16), trans‐ferulic acid (17) and 6‐Methoxyspirotryprostatin B (18). Anticancer evaluation study of all the compounds against a panel of eleven human tumor cell lines (PC‐3, HT‐29, MCF‐7, OVCAR‐5, HCT‐15, SF‐268, A549, HCT‐116, SW620, T47D and MD‐MBA‐435) of varied tissue origin revealed that compound 5 found to be the most potent cytotoxic agent against all the cancer cell lines examined, with an IC50 value <1.0 μM. But, it also showed cytotoxicity for normal human cells. Compounds 12, 14 and 15 exhibited maximum cytotoxicity against colon (HT‐29) cancer cell line with IC50 values 2.2, 2.8 and 7.7 μM respectively and were nontoxic for normal human cells. Docking studies of all the isolated compounds carried out using the Gaussian 09 suite of programs at B3LYP/6‐31+G(d) level of theory against three different proteins Poly [ADP‐ribose] polymerase‐1 (ID: 1UK0), TRAF2 (ID: 2X7F) and Matrix Metalloproteinase‐2 (ID: 1HOV) and maximum binding affinity was observed for TRAF2 (2X7F) protein. The in silico and in vitro anticancer results revealed that compounds 14 and 15 have the potential to be developed as anticancer agents against colon cancer cells.