Potent CYP17 inhibitors: improved syntheses, pharmacokinetics and anti-tumor activity in the LNCaP human prostate cancer model

Mechanism of antiproliferative action of a new d -secoestrone-triazole derivative in cervical cancer cells and its effect on cancer cell motility

“…The most frequent positions for substitution of the sterane skeleton are C-2, C-3 and C-17. Moreover, steroids with a triazole moiety in different positions have also been revealed to exert potent growth-inhibitory effects [25][26][27][28][29]. Furthermore, incorporating a triazole structure into the estrone skeleton may improve stability, solubility and bioavailability of the compound [30].…”

Exploration of new 3α-pregnenolone ester analogues via Mitsunobu reaction, their anti-HIV activity and molecular modeling study

“…In 1996, Njar et al [20,26] reported the first steroidal inhibitors of CYP17 bearing a heterocyclic moiety bound to C17 by a nitrogen atom, among which the imidazolyl derivative 1 was found to be the most promising [20][21][22][23][26][27][28][29]. Later, in 2005, the same group reported the synthesis of galeterone 2 and its Δ 4 -3-keto derivative [23][24][25][29][30][31], where compound 2 is currently undergoing Phase I/II clinical trials for the treatment of chemotherapy-naive CRPC [26,27,[32][33]. However, patients suffering from CRPC can clearly benefit from the newly approved drug abiraterone acetate (Zytiga) 3 [28,29,34,35].…”

“…Later, in 2005, the same group reported the synthesis of galeterone 2 and its Δ 4 -3-keto derivative [23][24][25][29][30][31], where compound 2 is currently undergoing Phase I/II clinical trials for the treatment of chemotherapy-naive CRPC [26,27,[32][33]. However, patients suffering from CRPC can clearly benefit from the newly approved drug abiraterone acetate (Zytiga) 3 [28,29,34,35]. This pregnenolone derivative was designed as an inhibitor of the enzyme 17α-hydroxylase/C17,20-lyase (CYP17A1) [30,36] which catalyzes two key reactions in steroid hormone biosynthesis.…”

A new pregnenolone analogues as privileged scaffolds in inhibition of CYP17 hydroxylase enzyme. Synthesis and in silico molecular docking study

“…In addition, computational studies established that a good inhibitor should possess a sufficiently large hydrophobic core, comparable to a steroid molecule, and bear electronegative groups at its external positions [10,11]. Therefore, recently several nitrogen containing steroidal compounds containing fiveor six-membered 17b-exo-heterocycles (preferably nitrogen containing), such as steroidal azoles [12,13] have been developed for the treatment of prostate cancer, including abiraterone acetate (Zytiga) 1 [14,15], VN/124-1 galeterone (2) [16][17][18], which is currently undergoing phase I/II clinical trials for the treatment of chemotherapy naive castration-resistant prostate cancer (CRPC) [19,20] and VN/85-1 (3) [21,22] (Fig. 1), which reduce circulating androgen levels through inhibition of CYP17 [23].…”