Synthesis, biological evaluation and X-ray analysis of bicalutamide sulfoxide analogues for the potential treatment of prostate cancer

The androgen receptor (AR) is a pivotal target for the treatment of prostate cancer (PC) even when disease progresses toward androgen-independent or castration-resistant forms. In this study, series sulfoxide derivatives were prepared and their antiproliferative activity evaluated in vitro against four different human cell lines (22Rv1, DU-145, LNCaP VCap). Bicalutamide enzalutamide used as positive controls. Compound 28 displayed significant enhancement anticancer across PC with IC50 = 9.09 – 31.11 µM compared to controls: bicalutamide (IC50 45.20 –51.61 µM) 11.47 53.04 µM). Sulfoxide efficiently from corresponding sulfides using only one equivalent mCPBA, limiting reaction time 15–30 min maintaining temperature at 0 °C. Interestingly, three pairs diastereomers separated NMR comparison diastereotopic methylene (CH2) group presented. X-ray diffraction crystal structure analysis provided relative configuration assignment chiral sulfur carbon centres. Molecular modelling study diastereoisomers compound described.