CYTOTOXIC AND ANTIPROLIFERATIVE STUDIES OF ISOCORDOIN AND SOME DERIVATIVES AGAINST PROSTATE CANCER CELL LINES

The proposed study was to evaluate the in-vitro cytotoxic and antiproliferative activities on prostate cancer cell lines of isocordoin (1) and 2’,4’-dihydroxy-3’-(g,g-dimethylallyl) dihydrochalcone (2), chalcones isolated from roots of Lonchocarpus xuul Lundel, together with four analogues of 1. Isolation of compounds 1 and 2 from L. xuul roots and chemical modification were in accordance with previous works. All compounds were characterized by NMR spectroscopy and mass spectrometry. In-vitro cytotoxic and antiproliferative activities of compounds 1-6 against prostate cancer cell lines PC3, PC3M, DU145, and TRAMPC2, were evaluated using the MTT and sulforhodamine B method, respectively. Additionally, cytotoxic studies with HEK 293 cells were carried out, and a selective index was calculated. From them 2’,4’-dihydroxy-3’-(g,g-dimethylallyl) dihydrochalcone (2), 2´,4´-diacetoxy-3´-(3-methylbut-2-enyl) chalcone (3), 2´-methoxy-3´-(3-methylbut-2-enyl) chalcone (5) together with isocordoin (1) showed the strongest cytotoxic activity on PC3M cell lines in the ranged of 2-3 mg/mL. Isocordoin showed the strongest activity also on TRAMPC2 cell lines (CC₅₀= 1.01 mg/mL). None of the compounds were cytotoxic (CC₅₀ =14 to 667 mg/mL) on HEK293 cell line. Xanthohumol, a natural active chalcone, and docetaxel were used as positive controls. The modifications made to isocordoin (1) in all cases reduced the cytotoxicity of this metabolite on HEK 293 cell lines; however, no antiproliferative properties were detected on compounds 1-6.