Synthesis of branched alkyl substituted phenylene derivatives as potential drug molecules active against prostate cancer

Abstract

Prostate cancer is the most common cancer type among male all around the world. Androgens are steroid based hormones which control the maintenance of male sex characteristics. It was found that high levels of androgens increase the risk of getting prostate cancer in some men and also promote the prostate cell growth. Therefore, reducing androgen level could be successful to suppress tumor growth. The two most important androgens are testosterone (T) and dihydrotestosterone (DHT). Amount of testosterone and dihydrotestosterone in blood is proportional to the androgen biosynthesis. Therefore, suppression of these androgens have been become the target of many studies which deal with the PC. Androgens are synthesized in both testes and adrenal glands. Therefore, to stop androgen biosynthesis it is necessary to inhibit the androgen biosynthesis in both testes and adrenal glands. CYP17 catalyzes, in testes and adrenals, the synthesis of both testosterone and DHT. Because of that reason CYP17 is the main target enzyme for the treatment of prostate cancer. CYP-17 inhibitors can be classified as steroidal and non-steroidal inhibitors. Non-steroidal compounds have advantages to the steroidal compounds. In this respect researchers in Koc University screened computationally about 50000 molecules and a non-steroidal lead molecule was determined. In this project, variations on the lead compound were done where mainly branched alkyl substituted phenylene rings and their couplings with available naphtoic acid derivatives were targeted. For this purpose 9 compounds were synthesized successfully and sent to the Koc University for biological testing.