CYTOTOXIC AND ANTIPROLIFERATIVE STUDIES OF ISOCORDOIN AND SOME DERIVATIVES AGAINST PROSTATE CANCER CELL LINESAbstract
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.
A. Yam-Puc, R. Borges-Argáez *, R. Moo-Puc and M. Cáceres Farfán
Unidad de Biotecnología, Centro de Investigación Científica de Yucatán, Calle 43 No. 130 Colonia Chuburná de Hidalgo CP 97200, Mérida, Yucatán, México.
09 August 2019
02 March 2021
19 May 2021
01 August 2021