values ranging from 4.32 to 6.47 µM against androgen receptor-negative PCa cell lines (PC3 and DU145). Compound OH16 potently suppressed colony formation and inhibited cell migration at 5 and 10 µM treatment concentrations. Additionally, OH16 effectively induced apoptosis, as evidenced by increased cleavage of Caspase-3 and PARP. The antiproliferative activity of compound OH16 is associated with the suppression of the ERK1/2 and Akt signaling pathways. Moreover, OH16 exhibited anti-angiogenic activity using the chorioallantoic membrane (CAM) of the chicken embryo model. Structure-activity relationship analysis of the synthesized analogs demonstrated that the tetralone ring is detrimental to activity, while the presence of the thienyl-pyridine ring highly enhances potency. Additionally, in silico ADMET screening showed that OH16 exhibits favorable predicted drug-likeness properties. These findings suggest that thienyl-pyridine-based chalcones may serve as promising lead compounds against CRPC; thus, further in vitro and in vivo studies are warranted.
Hussein et al. (Wed,) studied this question.