In continuation of the search for new natural compounds and their synthetic derivatives capable of overcoming the resistance of drug-resistant prostate cancer, we identified several 2-methoxy-1,4-naphthoquinones to be active in human prostate cancer PC-3 cells, known to be docetaxel-resistant and hormone-independent (due to the absence of AR expression) (compounds 1, 5, 9, 13, 17, 21, and 25; Tables S2 and S4). This evidence concerns the gene AR and prostate cancer.