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In order to find novel inhibitors of 17a-hydroxylase-17,20-lyase (cytochrome P450 17A1, CYP17A1), a key enzyme of biosynthesis of androgens, molecular docking of six new oxazoline-containing derivatives 17(20)E-pregna-5,17(20)-diene has been carried out to the active site of the crystal structure of CYP17A1 (pdb 3ruk). Results of this study indicate that: 1) complex formation of docked compounds with CYP17A1 causes their isomerization in energetically less favorable 17(20)Z-isomer; 2) the localization of the steroid moiety of all compounds in the active site is basically the same; 3) the structure of the oxazoline moiety significantly influences its position relative to heme as well as the energy of complex formation; 4) coordination of the nitrogen atom of the oxazoline moiety and the heme iron is only possible in the 17(20)Z-conformation with anti oriented double bonds 17(20), and C=N; 5) the presence of two substituents at C4' of the oxazoline moiety significantly impairs ligand binding; 6) oxazoline - and benzoxazole-containing derivatives 17(20)E-pregna-5,17(20)-diene can effectively inhibit the catalytic activity CYP17A1 and may be of interest as a basis for the development of new drugs for the treatment of androgen-dependent cancer.

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In order to find novel inhibitors of 17α hydroxylase 17,20 lyase (cytochrome P450 17A1, CYP17A1), a key enzyme of biosynthesis of androgens, molecular docking of six new oxazoline containing derivatives 17(20)E pregna 5,17(20) diene has been carried out to the active site of the crystal structure of CYP17A1 (pdb 3ruk). Results of this study indicate that: (1) complex formation of docked compounds with CYP17A1 causes their isomerization in energetically less favorable 17(20)Z isomer; (2) the localization of the steroid moiety of all compounds in the active site is basically the same; (3) the structure of the oxazoline moi ety significantly influences its position relative to heme as well as the energy of complex formation; (4) coor dination of the nitrogen atom of the oxazoline moiety and the heme iron is only possible in the 17(20)Z con formation with anti oriented double bonds 17(20), and C=N; (5) the presence of two substituents at C4' of the oxazoline moiety significantly impairs ligand binding; (6) oxazoline and benzoxazole containing deriv atives 17(20)E pregna 5,17(20) diene can effectively inhibit the catalytic activity CYP17A1 and may be of interest as a basis for the development of new drugs for the treatment of androgen dependent cancer.

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