Prostate cancer (PC) is the most common cancer in men around the word. It is a complex and heterogeneous disease in which androgens and their receptor play a crucial role in the progression and development. The current treatment for PC is a combination of surgery, radiation and chemotherapy. Therapeutic agents commonly used in the clinic include steroidal and non- steroidal antiandrogens, such as cyproterone acetate. These few agents have multiple adverse effects and are not 100% effective. Several plant compounds and mixtures, including grape seed polyphenol extracts, lycopene and tomato preparations, soy isoflavones, and green tea extracts, have been shown to be effective against PC cell growth. Some isolated compounds were reported with in vivo activity on CP murine model like capsaicin and curcumin. We prepared a library of plant extracts from traditional Mayan medicine. These plants were selected for their use in the contemporaneous Maya communities with application in different types of diseases and treatments. These extracts were used in a phenotypic screening in LNCaP (androgen sensitive) prostate cancer cells in a fixed dose (25 μg / mL). Ten plants out of 11 were identified with cytotoxic activity in these cells. With the active extracts, a bioguided fractionation method was performed until the elucidation of the major components. We identified 3 compounds with activity and design one hybrid molecule with the natural product structure and steroid analog to enhance the antiproliferative activity.