Evaluation of Extracts from Figonia critica and Organotin Derivatives as Potential Inhibitors of Multidrug Resistance ABCB1 Transporter

Abstract

Human P-glycoprotein (P-gp) belongs to the ABC transporter family. Physiologically, ABCB1 is renowned for exporting a wide variety of toxins and drugs outside the cell, thereby providing a shielding effect to the cells. Overexpression of ABCB1 mediates cancer cell resistance to cytotoxic drugs in cancer patients. In the current study, Organotin derivatives and phytochemicals from Figonia critica (flavonoids, alkaloids) were screened as potential inhibitors of ABCB1 in a cell proliferation assay. Additionally, Organotin derivatives were docked into the human-mouse chimera P-gp structure (PDB ID;6FN4) in order to predict their interactions with ABCB1. The common interacting residues in the binding cavity were found to be Gln990, Phe303, Met986, Phe335, and Met966. In conclusion, the three Organotin compounds SB3, SB4, and SB1 showed good potential to be developed into anticancer agents due to their strong cytotoxicity against CCRF-CEM VCR₁₀₀₀ by demonstrating IC50 values of 16.62±0.05µM, 16.88±0.21µM, and 18.93±0.007µM, respectively. In addition, the IC₅₀ values were also calculated for flavonoids and alkaloids as 22.07±0.05µg/mL and 18.07±0.08 µg/mL, respectively.  To our knowledge, this is the first report demonstrating both synthetic Organotin derivatives and natural phytochemicals from Fagonia critica as dual sources of potential ABCB1 inhibitors, offering new directions for overcoming multidrug resistance in cancer therapy.