Synthesis and molecular modeling of novel tetrahydro-β-carboline derivatives with phosphodiesterase 5 inhibitory and anticancer properties

Journal of Medicinal Chemistry

Volumn 54, Issue 2, 2011, Pages 495-509

  Mohamed, Heba A ^a   Girgis, Nancy M R ^a   Wilcken, Rainer ^b   Bauer, Matthias R ^b   Tinsley, Heather N ^c   Gary, Bernard D ^c   Piazza, Gary A ^c   Boeckler, Frank M ^b   Abadi, Ashraf H ^a  

^a German University in Cairo   (Egypt)

^b UNIVERSITY OF TÜBINGEN   (Germany)

^c UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

6 (2,4 DICHLOROPHENYL) 2 ETHYL 2,3,6,7,12,12A HEXAHYDROPYRAZINO[1' ,2':1,6]PYRIDO[3,4 B]INDOLE 1,4DIONE; ISOENZYME; PHOSPHODIESTERASE V; TETRAHYDRO BETA CARBOLINE HYDANTOIN; TETRAHYDRO BETA CARBOLINE PIPERAZINEDIONE; TRYPTOLINE DERIVATIVE; TRYPTOPHAN; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; BREAST TUMOR; DRUG POTENCY; DRUG SYNTHESIS; IC 50; MOLECULAR MODEL; TUMOR CELL LINE;

ANTINEOPLASTIC AGENTS; CARBOLINES; CELL LINE, TUMOR; CELL PROLIFERATION; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; MODELS, MOLECULAR; PHOSPHODIESTERASE 5 INHIBITORS; RECOMBINANT PROTEINS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 78751675559     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm100842v     Document Type: Article

References (24)

1. Conti, M.; Beavo, J. Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling Annu. Rev. Biochem. 2007, 76, 481-511
2. Omori, K.; Kotera, J. Overview of PDEs and their regulation Circ. Res. 2007, 16, 309-327
3. Ghofrani, H. A.; Osterloh, I. H.; Grimminger, F. Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and beyond Nature Rev. Drug Discovery 2006, 5, 689-702
4. Masson, P.; Lambert, S. M.; Brown, M.; Shabsigh, R. PDE-5 inhibitors: current status and future trends Urol. Clin. North Am. 2005, 32, 511-525
5. Watanabe, H.; Ohashi, K.; Takeuchi, K.; Yamashita, K.; Yokoyama, T.; Tran, Q. K.; Satoh, H.; Terada, H.; Ohashi, H.; Hayashi, H. Sildenafil for primary and secondary pulmonary hypertension Clin. Pharmacol. Ther. 2002, 71, 398-402
6. Tinsley, H. N.; Gary, B. D.; Keeton, A. B.; Zhang, W.; Abadi, A. H.; Reynolds, R. C.; Piazza, G. A. Sulindac sulfide selectively inhibits growth and induces apoptosis of human breast tumor cells by phosphodiesterase 5 inhibition, elevation of cyclic GMP and activation of protein kinase G Mol. Cancer Ther. 2009, 8, 3331-3340
7. Abadi, A. H.; Abouel-Ella, D. A.; Ahmed, N. S.; Gary, B. D.; Thaiparambil, J. T.; Tinsley, H. N.; Keeton, A. B.; Piazza, G. A. Synthesis of novel tadalafil analogues and their evaluation as phosphodiesterase inhibitors and anticancer agents Arzneim. Forsch. 2009, 59, 415-421
8. Jenkins, P. R.; Wilson, J.; Emmerson, D.; Garcia, M. D.; Smith, M. R.; Gray, S. J.; Britton, R. G.; Mahale, S.; Chaudhuri, B. Design, synthesis and biological evaluation of new tryptamine and tetrahydro-beta-carboline-based selective inhibitors of CDK4 Bioorg. Med. Chem. 2008, 16, 7728-7739
9. Leteurtre, F.; Madalengoitia, J.; Orr, A.; Guzi, T. J.; Lehnert, E.; Macdonald, T.; Pommier, Y. Rational design and molecular effects of a new topoisomerase II inhibitor, azatoxin Cancer Res. 1992, 52, 4478-4483
10. Sunder-Plassmann, N.; Sarli, V.; Gartner, M.; Utz, M.; Seiler, J.; Huemmer, S.; Mayer, T. U.; Surrey, T.; Giannis, A. Synthesis and biological evaluation of new tetrahydro-beta-carbolines as inhibitors of the mitotic kinesin Eg5 Bioorg. Med. Chem. 2005, 13, 6094-6111 (Pubitemid 41400131)
11. Doggrell, S. A. Comparison of clinical trials with sildenafil, vardenafil and tadalafil in erectile dysfunction Expert Opin. Pharmacother. 2005, 6, 75-84
12. Duan, H.; Zheng, J.; Lai, Q.; Liu, Z.; Tian, G.; Wang, Z.; Li, J.; Shen, J. 2-Phenylquinazolin-4(3 H)-one, a class of potent PDE5 inhibitors with high selectivity versus PDE6 Bioorg. Med. Chem. Lett. 2009, 19, 2777-2779
13. Al-Shaiji, T. F.; Brock, G. B. Phosphodiesterase type 5 inhibitors for the management of erectile dysfunction: preference and adherence to treatment Curr. Pharm. Des. 2009, 15, 3486-3495
14. Sung, B. J.; Hwang, K. Y.; Jeon, Y. H.; Lee, J. I.; Heo, Y. S.; Kim, J. H.; Moon, J.; Yoon, J. M.; Hyun, Y. L.; Kim, E.; Eum, S. J.; Park, S. Y.; Lee, J. O.; Lee, T. G.; Ro, S.; Cho, J. M. Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules Nature 2003, 425, 98-102
15. Ke, H.; Wang, H. Crystal structures of phosphodiesterases and implications on substrate specificity and inhibitor selectivity Curr. Top. Med. Chem. 2007, 7, 391-403
16. Zoraghi, R.; Francis, S. H.; Corbin, J. D. Critical amino acids in phosphodiesterase-5 catalytic site that provide for high-affinity interaction with cyclic guanosine monophosphate and inhibitors Biochemistry 2007, 46, 13554-13563
17. Whaley, W. M.; Govindachari, T. R. The Pictet-Spengler synthesis of tetrahydroisoquinolines and related compounds Org. React. 1951, 6, 151
18. Ungemach, F.; DiPierro, M.; Weber, R.; Cook, J. M. Stereospecific Synthesis of trans -1,3-Disubstituted-l,2,3,4-tetrahydro-β-carbolines J. Org. Chem. 1981, 46, 164-168
19. Cox, E. D.; Cook, J. M. The Pictet-Spengler condensation: a new direction for an old reaction Chem. Rev. 1995, 95, 1797-1842
20. b-diphenymethyl tryptophan isopropyl esters with aldehydes Tetrahedron Lett. 1992, 48, 4721-4724
21. Pulka, K.; Kulis, P.; Tymecka, D.; Frankiewicz, L.; Wilczek, M.; Kozminski, M.; Misicka, A. Diastereoselective Pictete-Spengler condensation of tryptophan with α-amino aldehydes as chiral carbonyl components Tetrahedron Lett. 2008, 64, 1506-1514
22. Sandrin, J.; Soerens, D.; Cook, J. M. Carbon-13 NMR of 1,3-Disubstituted 1,2,3,4-Tetrahydro-β-Carbolines Heterocycles 1976, 4, 1249-1255
23. Ungemach, F.; Soerens, D.; Weber, R.; DiPierro, M.; Campos, O.; Mokry, P.; Cook, J. M.; Silverton, J. V. General Method for the Assignment of Stereochemistry of 1,3-Disubstituted 1,2,3,4-Tetrahydro-β-Carbolines by Carbon-13 Spectroscopy J. Am. Chem. Soc. 1980, 102, 6976-6984
24. Zoraghi, R.; Corbin, J. D.; Francis, S. H. Phosphodiesterase-5 Gln817 is critical for cGMP, vardenafil, or sildenafil affinity: its orientation impacts cGMP but not cAMP affinity J. Biol. Chem. 2006, 281, 5553-5558