Synthesis, conformational analysis, and biological evaluation of 1-hexylindolactam-V10 as a selective activator for novel protein kinase C isozymes

Journal of Medicinal Chemistry

Volumn 51, Issue 1, 2008, Pages 46-56

  Yanagita, Ryo C ^a   Nakagawa, Yu ^a   Yamanaka, Nobuhiro ^a   Kashiwagi, Kaori ^b   Saito, Naoaki ^b   Irie, Kazuhiro ^a  

^a KYOTO UNIVERSITY   (Japan)

^b KOBE UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

1 HEXYLINDOLACTAM V10; 5 BROMO 1 HEXYLINDOLACTAM V10; 5 CHLORO 1 HEXYLINDOLACTAM V10; INDOLACTAM V; ISOENZYME; PROTEIN KINASE C; PROTEIN KINASE C ACTIVATOR; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ARTICLE; BIOLOGICAL ACTIVITY; CONTROLLED STUDY; DRUG CONFORMATION; DRUG PROTEIN BINDING; DRUG SCREENING; DRUG SELECTIVITY; DRUG SYNTHESIS; ENZYME ACTIVATION; HELA CELL; HUMAN; HUMAN CELL; REPERFUSION INJURY; STRUCTURE ACTIVITY RELATION; TUMOR PROMOTION;

CELL MEMBRANE; ENZYME ACTIVATORS; HELA CELLS; HUMANS; INDOLES; ISOENZYMES; LACTAMS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; MUTATION; PROTEIN BINDING; PROTEIN KINASE C; PROTEIN TRANSPORT; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 37849047968     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0706719     Document Type: Article

References (60)

1. Nishizuka, Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature 1984, 308, 693-698.
2. Nishizuka, Y. Protein kinase C and lipid signaling for sustained cellular responses. FASEB J. 1995, 9, 484-496.
3. Kazanietz, M. G.; Areces, L. B.; Bahador, A.; Mischak, H.; Goodnight, J.; Mushinski, J. F.; Blumberg, P. M. Characterization of ligand and substrate specificity for the calcium-dependent and calcium-independent protein kinase C isozymes. Mol. Pharmacol. 1993, 44, 298-307.
4. Fujiki, H.; Sugimura, T. New classes of tumor promoters: teleocidin, aplysiatoxin, and palytoxin. Adv. Cancer Res. 1987, 49, 223-264.
5. Griner, E. M.; Kazanietz, M. G. Protein kinase C and other diacylglycerol effectors in cancer. Nat. Rev. Cancer 2007, 7, 281-294.
6. 1 inhibits gastric carcinogenesis. Cancer Res. 2004, 64, 5787-5794.
7. Cacace, A. M.; Ueffing, M.; Philipp, A.; Han, E. K.; Kolch, W.; Weinstein, I. B. PKCε functions as an oncogene by enhancing activation of the Raf kinase. Oncogene 1996, 13, 2517-2526.
8. Mischak, H.; Goodnight, J.; Kolch, W.; Martiny-Baron, G.; Schaechtle, C.; Kazanietz, M. G.; Blumberg, P. M.; Pierce, J. H.; Mushinski, J. F. Overexpression of protein kinase C-δ and -ε in NIH 3T3 cells induces opposite effects on growth, morphology, anchorage dependence, and tumorigenicity. J. Biol. Chem. 1993, 268, 6090-6096.
9. Jackson, D. N.; Foster, D. A. The enigmatic protein kinase Cδ: complex roles in cell proliferation and survival. FASEB J. 2004, 18, 627-636.
10. Lu, Z.; Hornia, A.; Jiang, Y.-W.; Zang, Q.; Ohno, S.; Foster, D. A. Tumor promotion by depleting cells of protein kinase Cδ. Mol. Cell. Biol. 1997, 17, 3418-3428.
11. Reddig, P. J.; Dreckschimdt, N. E.; Ahrens, H.; Simsiman, R.; Tseng, C.; Zou, J.; Oberley, T. D.; Verma, A. K. Transgenic mice overexpressing protein kinase Cδ in the epidermis are resistant to skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate. Cancer Res. 1999, 59, 5170-5718.
12. Chida, K.; Hara, T.; Hirai, T.; Konishi, C.; Nakamura, K.; Nakao, K.; Aiba, A.; Katsuki, M.; Kuroki, T. Disruption of protein kinase Cη results in impairment of wound healing and enhancement of tumor formation in mouse skin carcinogenesis. Cancer Res. 2003, 63, 2404-2408.
13. Graff, J. R.; McNulty, A. M.; Hanna, K. R.; Konicek, B. W.; Lynch, R. L.; Bailey, S. N.; Banks, C.; Capen, A.; Goode, R.; Lewis, J. E.; Sams, L.; Huss, K. L.; Campbell, R. M.; Iversen, P. W.; Neubauer, B. L.; Brown, T. J.; Musib, L.; Geeganage, S.; Thornton, D. The protein kinase Cβ-selective inhibitor, enzastaurin (LY317615.HCl) suppress signaling through the AKT pathway, induces apoptosis, and suppress growth of human colon cancer and glioblastoma xenografts. Cancer Res. 2005, 65, 7462-7469.
14. Querfeld, C.; Rizvi, M. A.; Kuzel, T. M.; Guitart, J.; Rademaker, A.; Sabharwal, S. S.; Krett, N. L.; Rosen, S. T. The selective protein kinase Cβ inhibitor enzastaurin induces apoptosis in cutaneous T-cell lymphoma cell lines through the AKT pathway. J. Invest. Dermatol. 2006, 126, 1641-1647.
15. Budas, G. R.; Churchill, E. N.; Mochly-Rosen, D. Cardioprotective mechanisms of PKC isozyme-selective activators and inhibitors in the treatment of ischemia-reperfusion injury. Pharmacol. Res. 2007, 55, 523-536.
16. Zhu, G.; Wang, D.; Lin, Y.-H.; Mcmahon, T.; Koo, E. H.; Messing, R. O. Protein kinase C ε suppresses Aβ production and promotes activation of α-secretase. Biochem. Biophys. Res. Commun. 2001, 285, 997-1006.
17. Warwar, N.; Efendic, S.; Östenson, C.-G.; Haber, E. P.; Cerasi, E.; Nesher, R. Dynamics of glucose-induced localization of PKC isoenzymes in pancreatic β-cells. Diabetes 2006, 55, 590-599.
18. Endo, Y.; Shudo, K.; Okamoto, T. Molecular requirements for epigenetic modulators. Synthesis of active fragments of teleocidins and lyngbyatoxin. Chem. Pharm. Bull. 1982, 30, 3457-3460.
19. Irie, K.; Hirota, M.; Hagiwara, N.; Koshimizu, K.; Hayashi, H.; Murao, S.; Tokuda, H.; Ito, Y. The Epstein-Barr virus early antigen inducing indole alkaloids, (-)-indolactam V and its related compounds produced by actinomycetes. Agric. Biol. Chem. 1984, 48, 1269-1274.
20. Ma, D.; Tang, G.; Kozikowski, A. P. Synthesis of 7-substituted benzolactam-V8s and their selectivity for protein kinase C isozymes. Org. Lett. 2002, 4, 2377-2380.
21. Nakagawa, Y.; Irie, K.; Komiya, Y.; Ohigashi, H.; Tsuda, K. Synthesis, conformation and PKC isozyme surrogate binding of indolinelactam-Vs, new conformationally restricted analogues of (-)-indolactam-V. Tetrahedron 2004, 60, 7077-7084.
22. Nakagawa, Y.; Irie, K.; Yanagiata, R. C.; Ohigashi, H.; Tsuda, K.; Kashiwagi, K.; Saito, N. Design and synthesis of 8-octyl-benzolactam-V9, a selective activator for protein kinase Cε and η. J. Med. Chem. 2006, 49, 2681-2688.
23. Nishio, M.; Hirota, M.; Umezawa, Y. The CH/π Interaction. Evidence, Nature, and Consequences; Wiley-VCH: New York, 1998.
24. Endo, Y.; Takehana, S.; Ohno, M.; Driedger, P. E.; Stabel, S.; Mizutani, M. Y.; Tomioka, N.; Itai, A.; Shudo, K. Clarification of the binding mode of teleocidin and benzolactams to the Cys2 domain of protein kinase Cδ by synthesis of hydrophobically modified, teleocidin-mimicking benzolactams and computational docking simulation. J. Med. Chem. 1998, 41, 1476-1496.
25. Nakagawa, Y.; Irie, K.; Yanagita, R. C.; Ohigashi, H.; Tsuda, K. Indolactam-V is involved in the CH/π interaction with Pro-11 of the PKCδ C1B domain: application for the structural optimization of the PKCδ ligand. J. Am. Chem. Soc. 2005, 127, 5746-5747.
26. Mizoroki, T.; Mori, K.; Ozaki, A. Arylation of olefin with aryl iodide catalyzed by palladium. Bull. Chem. Soc. Jpn. 1971, 44, 581.
27. Plevyak, J. E.; Heck, R. F. Palladium-catalyzed arylation of ethylene. J. Org. Chem. 1978, 43, 2454-2456.
28. Collier, P. N.; Patel, I.; Taylor, R. J. K. Heck reactions of amino acid building blocks: application to the synthesis of pyrrololine analogues. Tetrahedron Lett. 2002, 43, 3401-3405.
29. Collier, P. N.; Campbell, A. D.; Patel, I.; Raynham, T. M.; Taylor, R. J. K. Enantiomerically pure α-amino acid synthesis via hydroboration - Suzuki cross-coupling. J. Org. Chem. 2002, 67, 1802-1815.
30. Kogan, T. P.; Somers, T. C.; Venuti, M. C. A regio- and stereocontrolled total synthesis of (-)-indolactam-V. Tetrahedron 1990, 46, 6623-6632.
31. Endo, Y.; Shudo, K.; Itai, A.; Hasegawa, M.; Sakai, S. Synthesis and stereochemistry of indolactam-V, an active fragment of teleocidins. Structural requirements for tumor promoter activity. Tetrahedron 1986, 42, 5905-5924.
32. Kawai, T.; Ichinose, T.; Takeda, M.; Tomioka, N.; Endo, Y.; Yamaguchi, K.; Shudo, K.; Itai, A. Prediction of ring conformations of indolactams. Crystal and solution structures. J. Org. Chem. 1992, 57, 6150-6155.
33. Endo, Y.; Ohno, M.; Hirano, M.; Itai, A.; Shudo, K. Synthesis, conformation, and biological activity of teleocidin mimics, benzolactams. A clarification of the conformational flexibility problem in structure-activity studies of teleocidins. J. Am. Chem. Soc. 1996, 118, 1841-1855.
34. Irie, K.; Isaka, T.; Iwata, Y.; Yanai, Y.; Nakamura, Y.; Koizumi, F.; Ohigashi, H.; Wender, P. A.; Satomi, Y.; Nishino, H. Synthesis and biological activities of new conformationally restricted analogues of (-)-indolactam-V: elucidation of the biologically active conformation of the tumor-promoting teleocidins. J. Am. Chem. Soc. 1996, 118, 10733-10743.
35. Kozikowski, A. P.; Ma, D.; Pang, Y.; Shum, P.; Likic, V.; Mishra, P. K.; Macura, S.; Basu, A.; Kazo, J. S.; Ball, R. G. Synthesis, molecular modeling, 2-D NMR, and biological evaluation of ILV mimics as potential modulators of protein kinase C. J. Am. Chem. Soc. 1993, 115, 3957-3965.
36. Irie, K.; Oie, K.; Nakahara, A.; Yanai, Y.; Ohigashi, H.; Wender, P. A.; Fukuda, H.; Konishi, H.; Kikkawa, U. Molecular basis for protein kinase C isozyme-selective binding: the synthesis, folding, and phorbol ester binding of the cysteine-rich domains of all protein kinase C isozymes. J. Am. Chem. Soc. 1998, 120, 9159-9167.
37. Shindo, M.; Irie, K.; Nakahara, A.; Ohigashi, H.; Konishi, H.; Kikkawa, U.; Fukuda, H.; Wender, P. A. Toward the identification of selective modulators of protein kinase C (PKC) isozymes: establishment of a binding assay for PKC isozymes using synthetic C1 peptide receptors and identification of the critical residues involved in the phorbol ester binding. Bioorg. Med. Chem. 2001, 9, 2073-2081.
38. Szallasi, Z.; Bogi, K.; Gohari, S.; Biro, T.; Acs, P.; Blumberg, P. M. Non-equivalent roles for the first and second zinc fingers of protein kinase Cδ. J. Biol. Chem. 1996, 271, 18299-18301.
39. Hunn, M.; Quest, A. F. G. Cysteine-rich regions of protein kinase Cδ are functionally non-equivalent. Differences between cysteine-rich regions of non-calcium-dependent protein kinase Co and calcium-dependent protein kinase Cγ. FEBS Lett. 1997, 400, 226-232.
40. Irie, K.; Nakagawa, Y.; Ohigashi, H. Indolactam and benzolactam compounds as new medicinal leads with binding selectivity for C1 domains of protein kinase C isozymes. Curr. Pharm. Des. 2004, 10, 1371-1385.
41. 3H]phorbol 12,13-dibutyrate binding. Cancer Res. 1985, 45, 19-24.
42. Quest, A. F. G.; Bell, R. M. The regulatory region of protein kinase Cγ. Studies of phorbol ester binding to individual and combined functional segments expressed as glutathione S-transferase fusion proteins indicate a complex mechanism of regulation by phospholipids, phorbol esters, and divalent cations. J. Biol. Chem. 1994, 269, 20000-20012.
43. 2+ and diacylglycerol. Biochem. J. 2003, 370, 901-912.
44. Masuda, A.; Irie, K.; Nakagawa, Y.; Ohigashi, H. Binding selectivity of conformationally restricted analogues of (-)-indolactam-V to the C1 domains of protein kinase C isozymes. Biosci. Biotechnol. Biochem. 2002, 66, 1615-1617.
45. Harigai, M.; Kataoka, M.; Imamoto, Y. A single CH/π interaction weak hydrogen bond governs stability and the photocycle of the photoactive yellow protein. J. Am. Chem. Soc. 2006, 128, 10646-10647.
46. Umezawa, K.; Kawakami, M.; Watanabe, T. Molecular design and biological activities of protein-tyrosine phosphatase inhibitors. Pharmacol. Ther. 2003, 99, 15-24.
47. 1 receptor antagonists; preliminary investigation on their second "touch point". Eur. J. Med. Chem. 2005, 40, 563-581.
48. Matsushima, A.; Fujita, T.; Nose, T.; Shimohigashi, Y. Edge-to-face CH/π interaction between ligand Phe-phenyl and receptor aromatic group in the thrombin receptor activation. J. Biochem. 2000, 128, 225-232.
49. Irie, K.; Hayashi, H.; Arai, M.; Koshimizu, K. Substitution reaction on the indole ring of (-)-indolactma-V, the fundamental structure of teleocidins. Agric. Biol. Chem. 1986, 50, 2679-2680.
50. Irie, K.; Hagiwara, N.; Koshimizu, K. New probes for receptor analysis of tumor promoters; synthesis of fluorescent derivatives of (-)-indolactam-V, the basic ring-structure of teleocidins. Tetrahedron 1987, 43, 5251-5260.
51. Okuno, S.; Irie, K.; Suzuki, Y.; Koshimizu, K.; Nishino, H.; Iwashima, A. Synthesis and biological activities of fluorine-substituted (-)-indolactam-V, the core structure of tumor promoter teleocidins. Bioorg. Med. Chem. Lett. 1994, 4, 431-434.
52. Irie, K.; Hagiwara, N.; Tokuda, H.; Koshimizu, K. Structure-activity studies of the indole alkaloid tumor promoter teleocidins. Carcinogenesis 1987, 8, 547-552.
53. Jones, G.; Willett, P.; Glen, R. C. Molecular recognition of receptor sites using a genetic algorithm with a description of desolvation. J. Mol. Biol. 1995, 245, 43-53.
54. Kraft, A. S.; Anderson, W. B.; Cooper, H. L.; Sando, J. J. Decrease in cytosolic calcium/phoshpolipid-dependent protein kinase activity following phorbol ester treatment of EL4 thymoma cells. J. Biol. Chem. 1982, 257, 13193-13196.
55. Garcia-Bermejo, M. L.; Leskow, F. C.; Fujii, T.; Wang, Q.; Blumberg, P. M.; Ohba, M.; Kuroki, T.; Han, K.-C.; Lee, J.; Marquez, V. E.; Kazanietz, M. G. Diacylglycerol (DAG)-lactones, a new class of protein kinase C (PKC) agonists, induce apoptosis in LNCaP prostate cancer cells by selective activation of PKCα. J. Biol. Chem. 2002, 277, 645-655.
56. Sakai, N.; Sasaki, K.; Ikegaki, N.; Shirai, Y.; Ono, Y.; Saito, N. Direct visualization of the translocation of the γ-subspecies of protein kinase C in living cells using fusion proteins with green fluorescent protein. J. Cell Biol. 1997, 139, 1465-1476.
57. Wang, Q. J.; Bhattacharyya, D.; Garfield, S.; Nacro, K.; Marquez, V. E.; Blumberg, P. M. Differential localization of protein kinase Cδ by phorbol esters and related compounds using a fusion protein with green fluorescent protein. J. Biol. Chem. 1999, 274, 37233-37239.
58. Ohmori, S.; Sakai, N.; Shirai, Y.; Yamamoto, H.; Miyamoto, E.; Shimizu, H.; Saito, N. Importance of protein kinase C targeting for the phosphorylation of its substrate, myristoylated alanine-rich C-kinase substrate. J. Biol. Chem. 2000, 275, 26449-26457.
59. Sakuma, M. Probit analysis of preference data. Appl. Entomol. Zool. 1998, 33, 339-347.
60. Zhang, G.; Kazanietz, M. G.; Blumberg, P. M.; Hurley, J. H. Crystal structure of cys2 activator-binding domain of protein kinase Cδ in complex with phorbol ester. Cell 1995, 81, 917-924.