Derivatives of pyrimidine, phthalimide and anthranilic acid as inhibitors of human hydroxysteroid dehydrogenase AKR1C1

Chemico-Biological Interactions

Volumn 178, Issue 1-3, 2009, Pages 158-164

  Brozic P ^a   Cesar, J ^a   Kovac A ^a   Davies, M ^b   Johnson, A P ^b   Fishwick, C W G ^b   Lanisnik Rizner T ^a   Gobec, S ^a  

^a UNIVERSITY OF LJUBLJANA   (Slovenia)

^b UNIVERSITY OF LEEDS   (United Kingdom)

Author keywords

3 ,5 Tetrahydroprogesterone; AKR1C1; Inhibitors; Progesterone

Indexed keywords

2 (4 METHOXYBENZYL) 4 METHYL 6 PHENETHOXYPYRIMIDINE; 2 (4 METHOXYBENZYL) 6 METHYLPYRIMIDIN 4(3H) ONE; 2 [2 (4 METHOXYBENZYL) 6OXO 1,6 DIHYDROPYRIMIDIN 4 YL]ACETIC ACID; 2 [2 [2 (4 METHOXYBENZYL) 6 OXO 1,6 DIHYDROPYRIMIDIN 4 YL]ACETAMIDO]PROPANOIC ACID; 2 [[(2',3 DICHLOROBIPHENYL 4 YL)CARBONYL](METHYL)AMINO]BENZOIC ACID; 4 (BENZYLOXY) 2 (4 METHOXYBENZYL) 6 METHYLPYRIMIDINE; ANTHRANILIC ACID DERIVATIVE; BENZYL 2 [2 [2 (4 METHOXYBENZYL) 6 OXO 1,6 DIHYDROPYRIMIDIN 4 YL]ACETAMIDO]PROPANOATE; BUTYL 3 (1,3 DIOXOISOINDOLIN 2 YL)PROPANOATE; ETHYL 2 [2 (4 METHOXYBENZYL) 6 OXO 1,6 DIHYDROPYRIMIDIN 4 YL]ACETATE; HYDROXYSTEROID DEHYDROGENASE; HYDROXYSTEROID DEHYDROGENASE AKR1C1; N (3,4 DIMETHOXYPHENETHYL) 2 (4 METHOXYBENZYL) 6 METHYLPYRIMIDIN 4 AMINE; N BENZYL 2 (4 METHOXYBENZYL) 6 METHYLPYRIMIDIN 4 AMINE; N BENZYL 2 [2 (4 METHOXYBENZYL) 6 OXO 1,6 DIHYDROPYRIMIDIN 4 YL]ACETAMIDE; PHTHALIMIDE DERIVATIVE; PYRIMIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CATALYSIS; DRUG SYNTHESIS; ENZYME INHIBITION; OXIDATION; PROTEIN EXPRESSION;

20-HYDROXYSTEROID DEHYDROGENASES; ANTHRANILIC ACIDS; ENZYME INHIBITORS; HUMANS; KINETICS; MAGNETIC RESONANCE SPECTROSCOPY; MODELS, MOLECULAR; PHTHALIMIDES; PYRIMIDINES; RECOMBINANT PROTEINS; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION; SUBSTRATE SPECIFICITY;

EID: 59049099037     PISSN: 00092797     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cbi.2008.10.019     Document Type: Article

References (35)

1. Nobel S., Abrahmsen L., and Oppermann U. Metabolic conversion as a pre-receptor control mechanism for lipophilic hormones. Eur. J. Biochem. 268 (2001) 4113-4125
2. Penning T.M. Hydroxysteroid dehydrogenases and pre-receptor regulation of steroid hormone action. Hum. Reprod. Update 9 (2003) 193-205
3. Penning T.M. Molecular endocrinology of hydroxysteroid dehydrogenases. Endocr. Rev. 18 (1997) 281-305
4. Peltoketo H., Luu-The V., Simard J., and Adamski J. 17β-Hydroxysteroid dehydrogenase (HSD)/17-ketosteroid reductase (KSR) family; nomenclature and main characteristics of the 17HSD/KSR enzymes. J. Mol. Endocrinol. 23 (1999) 1-11
5. Mindnich R., Moeller G., and Adamski J. The role of 17beta-hydroxysteroid dehydrogenases. Mol. Cell. Endorinol. 218 (2004) 7-20
6. Möller G., and Adamski J. Multifunctionality of human 17β-hydroxysteroid dehydrogenases. Mol. Cell. Endorinol. 248 (2006) 47-55
7. Adamski J., and Jakob F.J. A guide to 17β-hydroxysteroid dehydrogenases. Mol. Cell. Endocrinol. 171 (2001) 1-4
8. Penning T.M., Burczynski M.E., Jez M.E., Hung C.F., Lin H.K., Ma H., Moore M., Palackal N., and Ratnam K. Human 3α-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C4) of the aldo-keto reductase superfamily: functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex steroids. Biochem. J. 351 (2000) 67-77
9. Penning T.M., and Drury J.E. Human aldo-keto reductases: function, gene regulation, and single nucleotide polymorphisms. Arch. Biochem. Biophys. 464 (2007) 241-250
10. Steckelbroeck S., Jin Y., Gopishetty S., Oyesanmi B., and Penning T.M. Human cytosolic 3α-hydroxysteroid dehydrogenases of the aldo-keto reductase superfamily display significant 3β-hydroxysteroid dehydrogenase activity: implications for steroid hormone metabolism and action. J. Biol. Chem. 279 (2004) 10784-10795
11. Lanišnik Rižner T., Lin H.K., Peehl D.M., Steckelbroeck S., Bauman D.R., and Penning T.M. Role of human type 3 3α-hydroxysteroid dehydrogenase (AKR1C2) in androgen metabolism of prostate cells. Endocrinology 144 (2003) 2922-2932
12. Dufort I., Labrie F., and Luu V. Human types 1 and 3 3α-hydroxysteroid dehydrogenases: differential liability and tissue distribution. J. Clin. Endocrinol. Metab. 86 (2001) 841-846
13. Griffin L.D., and Mellon S.H. Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes. Proc. Natl. Acad. Sci. USA 96 (1999) 13512-13517
14. Higaki Y., Usami N., Shintani S., Ishikura S., El-Kabbani O., and Hara A. Selective and potent inhibitors of human 20α-hydroxysteroid dehydrogenase (AKR1C1) that metabolizes neurosteroids derived from progesterone. Chem. Biol. Interact. 143-144 (2003) 503-513
15. Ji Q., Aoyama C., Nien Y.D., Liu P.I., Chen P.K., Chang L., Stanczyk F.Z., and Stolz A. Selective loss of AKR1C1 and AKR1C2 in breast cancer and their potential effect on progesterone signaling. Cancer Res. 64 (2004) 7610-7617
16. Lanišnik Rižner T., Šmuc T., Rupreht R., Šinkovec J., and Penning T.M. AKR1C1 and AKR1C3 may determine progesterone and estrogen ratios in endometrial cancer. Mol. Cell. Endocrinol. 248 (2006) 126-135
17. Brožič P., Šmuc T., Gobec S., and Lanišnik Rižner T. Phytoestrogens as inhibitors of the human progesterone metabolizing enzyme AKR1C1. Mol. Cell. Endocrinol. 259 (2006) 30-42
18. Usami N., Yamamoto T., Shintani S., Higaki Y., Ishikura S., Katagiri Y., and Hara A. Substrate specificity of human 3(20)α-hydroxysteroid dehydrogenase for neurosteroids and its inhibition by benzodiazepines. Biol. Pharm. Bull. 25 (2002) 441-445
19. Bauman D.R., Rudnick S., Szewczuk L.M., Jin Y., Gopishetty S., and Penning T.M. Development of non-steroidal anti-inflammatory drug (NSAID) analogues and steroid carboxylates selective for human aldo-keto reductase isoforms: potential antineoplastic agents that work independently of cyclooxygenase isozymes. Mol. Pharmacol. 67 (2005) 60-68
20. Byrns M.C., Steckelbroeck S., and Penning T.M. An indomethacin analogue, N-(4-chlorobezoyl)-melatonin, is a selective inhibitor of aldo-keto reductase 1C3 (type 2 3α-HSD, type 5 17β-HSD, and prostaglandin F synthase), a potential target for the treatment of hormone-dependent and hormone-independent malignancies. Biochem. Pharmacol. 75 (2008) 484-493
21. Dhagat U., Carbone V., Chung R.P.T., Matsunaga T., Endo S., Hara A., and El-Kabbani O. A salicylic acid-based analogue discovered from virtual screening as a potent inhibitor of human 20α-hydroxysteroid dehydrogenase. Med. Chem. 3 (2007) 546-550
22. P. Brožič, S. Turk, T. Lanišnik Rižner, S. Gobec, Discovery of new inhibitors of aldo-keto reductase 1C1 by structure-based virtual screening, Mol. Cell. Endocrinol., in press.
23. R.T.K. Cornwell, Composition capable of being molded and cast into films, US2487105 (1949).
24. Daraji R.R., and Shah A. Photochemical and thermal transformations of O-alkyl S-phthalylglycyl xanthates. Indian J. Chem. B 24B (1985) 685-686
25. Darji R.R., and Shah A. Photochemical and thermal transformations of unsymmetrical O,O-dialkyl S,S-phthaloyl dixanthates. Indian J. Chem. B 23B (1984) 509-511
26. Heikkila T., Thrumalairajan S., Davies M., Johnson A.P., McConkey G., and Fishwick C.W.G. The first de novo designed inhibitors of plasmodium falciparum dihydroorotate dehydrogenase. Bioorg. Med. Chem. Lett. 16 (2006) 88-92
27. Aroyan A.A., and Melik-Ogandzhanyan R.G. Synthesis of some imino ethers, amidines, and 4,6-dihydroxy- and 4,6-dichloro-2-(4-alkoxybenzyl)pyrimidines. Armyanskii Khimicheskii Zhurnal 20 (1967) 314-321 CAN 68: 29669
28. Aroyan A.A., Melik-Ogandzhanyan R.G., Khachatryan V.E., and Mirzoyan R.G. Pyrimidine derivatives. XXXIV. Synthesis of some 4-substituted 2-(4′-alkoxybenzyl)-6-methylpyrimidines. Armyanskii Khimicheskii Zhurnal 27 (1974) 428-433 CAN 81: 105434
29. Couture J.F., Cantin L., Legrand P., Luu-The V., Labrie F., and Breton R. Expression, crystallization and preliminary X-ray analysis of human and rabbit 20α-hydroxysteroid dehydrogenases in complex with NADP(H) and various steroid substrates. Acta Cryst. D 58 (2002) 135-139
30. Morris G.M., Goodsell D.S., Halliday R.S., Huey R., Hart W.E., Belew R.K., and Olson A.J. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J. Comp. Chem. 19 (1998) 1662-1693
31. Weiner S.J., Kollman P.A., Case D.A., Singh U.C., Ghio C., Alagona G., Profeta S., and Weiner P. A new force-field for molecular mechanical simulation of nucleic acids and proteins. J. Am. Chem. Soc. 106 (1984) 765-784
32. Gasteiger J., and Marsili M. Iterative partial equalization of orbital electronegativity - a rapid access to atomic charges. Tetrahedron 36 (1980) 3219-3228
33. Mehler E.L., and Solmajer T. Electrostatic effects in proteins - comparison of dielectric and charge models. Protein Eng. 4 (1991) 903-910
34. Hoffmann M.G., Nowak A., and Müller M. Pyrimidines. In: Schaumann E. (Ed). Methods of Organic Chemistry (Houben-Weyl) Vol. E9b/Part 1 (1998), Hetarenes IV, Georg Thieme Verlag, Stuttgart pp. 1-249
35. Luo G., Chen L., and Poindexter G.S. Microwave-assisted synthesis of aminopyrimidines. Tetrahedron Lett. 43 (2002) 5739-5742