Quinic acid from Annona muricata fruit inhibits cyclophosphamide metabolism through modulation of cytochrome P450: Implications for herbal-drug interaction

The oxazaphosphorine alkylating drugs, cyclophosphamide and its structural isomer, ifosamide, are frequently employed in the field of oncology for cancer treatment and immunosuppression purposes. An effective treatment method against cyclophosphamide toxicity has been suggested using plant extracts with high levels of antioxidant constituents. This study evaluates in vitro anticancer activity and anticipates the potential of quinic acid from A. muricata fruit to impact cyclophosphamide metabolism using CYP 450 isoenzyme inhibition. The phytochemicals in the ethanolic extract of A. muricata fruit were initially identified and validated using Q-TOF LC-MS. The MTT assay, a widely used method in cancer research, was employed to assess the potential anticancer activity against MCF-7 cancer cell lines in an in vitro setting. In molecular docking, one of the isolated compounds, quinic acid, was therefore indented to be docked with CYP-450 proteins. In Q-TOF LC/MS analysis, the different peaks were obtained at different retention times, and the quinic acid was at the retention time of 3.1 minutes. The extract showed remarkable in vitro anticancer activity (IC₅₀ value of 240.709 μg/mL) against MCF-7 cancer cell lines. The molecular docking study showed the most effective inhibition on CYP 3A4, CYP 2D6, CYP 2B6 and CYP 2C9 proteins, which indicated the interaction of quinic acid with CYP proteins and herbal drug interaction.