Synthesis and biological activity of progesterone derivatives as 5α-reductase inhibitors, and their effect on hamster prostate weight

Figures & data

Figure 1.  Reference compounds and their structures: 1, testosterone; 2, dihydrotestosterone; 3, finasteride; 4; dutasteride; 5, mibolerone.

Figure 2.  Synthesis of compounds 7–10. Reagents and conditions: (i) chloranil, AcOH, toluene, reflux 4 h; (ii) m-chloroperbenzoic acid (mCPBA), benzene, reflux 4 h; (iii) HCl, Ac₂O, 24 h, room temperature; (iv) NaOH, MeOH, reflux 2 h.

Table 1.  In vitro experiment.

Compound	Steroid structure	IC50 (nM)
3		8.5
6		10
7		70
8		22
9		19
10		NA

Note. IC₅₀ values were determined for finasteride 3 and synthesized steroids 6–10 with human prostate 5α-reductase enzyme. They represent the concentration of steroid that inhibits 50% of 5α-reductase activity and were determined as described in the “Experimental” section. NA, not active.

Figure 3.  Weight of prostate (± standard deviation) obtained from groups of castrated hamsters (four animals/group) receiving different subcutaneous treatments for 6 days. The control animals (C) were treated with vehicle only. The pharmacological experiment was carried out in duplicate. T, testosterone; 3, finasteride. *Weight of prostate decreased significantly (p < 0.05) as compared to that of T-treated animals.