Abstract

Cancer remains a major global health challenge, driving the search for novel anticancer agents from natural sources. Endophytic fungi associated with medicinal plants, particularly red ginger (Zingiber officinale Roscoe var. rubrum), represent promising reservoirs of bioactive metabolites with cytotoxic potential. In this study, the cytotoxic activity of ethyl acetate extracts obtained from endophytic fungi isolated from red ginger was evaluated. Preliminary screening using the brine shrimp lethality test identified potent extracts with lethal concentration values below 100 ppm. These active extracts were subsequently assessed for cytotoxicity against the human breast cancer cell line Michigan Cancer Foundation-7 using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Among the tested isolates, ZOBT1 exhibited notable cytotoxicity, with an inhibitory concentration value of 20.103 μg/ml. Molecular characterization confirmed the fungal isolate as Aspergillus niger ZOBT1. Furthermore, molecular docking analysis revealed that Fonsecinone A, a compound derived from this isolate, demonstrated stable interactions with key residues at the estrogen receptor (ER) binding site. Specifically, Fonsecinone A interacted with Trp393, a residue adjacent to the canonical ER binding site, yielding a docking score of −5.3536 kcal/mol and a root mean square deviation_refine of 1.7373 Å, suggesting a plausible mechanism for its anticancer activity. Overall, these findings highlight the potential of red ginger-associated endophytic fungi as promising sources of bioactive metabolites with anticancer properties, emphasizing the need for further pharmacological and mechanistic studies to validate their therapeutic relevance.

Key words: Zingiber officinale Roscoe var. rubrum, Fonsecinone A, Cytotoxicity, Molecular docking, Natural anticancer agent