5,5′-substituted indirubin-3′-oxime derivatives as potent cyclin-dependent kinase inhibitors with anticancer activity

Journal of Medicinal Chemistry

Volumn 53, Issue 9, 2010, Pages 3696-3706

  Choi, Soo Jeong ^a   Lee, Jung Eun ^a   Jeong, Soon Young ^b   Im, Isak ^a   Lee, So Deok ^a   Lee, Eun Jin ^c   Lee, Sang Kook ^c   Kwon, Seong Min ^d   Ahn, Sang Gun ^d   Yoon, Jung Hoon ^d   Han, Sun Young ^e   Kim, Jae Il ^a,b   Kim, Yong Chul ^a,b  

^a Gwangju Institute of Science and Technology (GIST)   (South Korea)

^b Division of Drug Discovery   (South Korea)

^c Ewha Womans University   (South Korea)

^d Chosun University   (South Korea)

^e Korea Research Institute of Chemical Technology   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

5 CHLORO 5' CHLORO INDIRUBIN 3' OXIME; 5 CHLORO 5' FLUORO INDIRUBIN 3' OXIME; 5 CHLORO 5' HYDROXY INDIRUBIN 3' OXIME; 5 CHLORO 5' METHYL INDIRUBIN 3' OXIME; 5 FLUORO 5' CHLORO INDIRUBIN 3' OXIME; 5 FLUORO 5' FLUORO INDIRUBIN 3' OXIME; 5 FLUORO 5' HYDROXY INDIRUBIN 3' OXIME; 5 FLUORO 5' METHYL INDIRUBIN 3' OXIME; 5 NITRO 5' CHLORO INDIRUBIN 3' OXIME; 5 NITRO 5' FLUORO INDIRUBIN 3' OXIME; 5 NITRO 5' HYDROXY INDIRUBIN 3' OXIME; 5 NITRO 5' METHYL INDIRUBIN 3' OXIME; 5 TRIFLUOROMETHOXY 5' CHLORO INDIRUBIN 3' OXIME; 5 TRIFLUOROMETHOXY 5' FLUORO INDIRUBIN 3' OXIME; 5 TRIFLUOROMETHOXY 5' HYDROXY INDIRUBIN 3' OXIME; 5 TRIFLUOROMETHOXY 5' METHYL INDIRUBIN 3' OXIME; ADENOSINE TRIPHOSPHATE; CYCLIN DEPENDENT KINASE 2; CYCLIN DEPENDENT KINASE INHIBITOR; CYCLIN E; HALOGEN; HYDROXYL GROUP; INDIRUBIN; INDOLE DERIVATIVE; OXIME DERIVATIVE; ROSCOVITINE; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; CDK2 PROTEIN, HUMAN; OXIME;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; BINDING SITE; CANCER CELL CULTURE; CELL PROLIFERATION; CONTROLLED STUDY; DRUG DESIGN; DRUG INHIBITION; DRUG POTENCY; DRUG SELECTIVITY; DRUG SOLUBILITY; DRUG SYNTHESIS; ENZYME ACTIVITY; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; PROTEIN PROTEIN INTERACTION; RAT; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION; TUMOR; CHEMISTRY; DRUG ANTAGONISM; TUMOR CELL LINE;

ADENOSINE TRIPHOSPHATE; ANTINEOPLASTIC AGENTS; BINDING SITES; CELL LINE, TUMOR; CYCLIN-DEPENDENT KINASE 2; CYCLIN-DEPENDENT KINASE INHIBITOR PROTEINS; DRUG DESIGN; HUMANS; INDOLES; OXIMES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 77952054912     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm100080z     Document Type: Article

References (41)

1. Harper, J. W.; Adams, P. D. Cyclin-dependent kinases Chem. Rev. 2001, 101, 2511-2526
2. Morgan, D. O. Principles of CDK regulation Nature 1995, 374, 131-134
3. Dyson, N. The regulation of E2F by pRB-family proteins Genes Dev. 1998, 12, 2245-2262
4. Weinberg, R. A. The retinoblastoma protein and cell cycle control Cell 1995, 81, 323-330
5. Chen, Y. N. P.; Sharma, S. K.; Ramsey, T. M.; Jiang, L.; MartM. S.; Baker, K.; Adams, P. D.; Bair, K. W.; KaelW. G., Jr. Selective killing of transformed cells by cyclin/cyclin-dependent kinase 2 antagonists Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 4325-4329
6. Shapiro, G. I.; Harper, J. W. Anticancer drug targets: cell cycle and checkpoint control J. Clin. Invest. 1999, 104, 1645-1653
7. Van Den Heuvel, S.; Harlow, E. Distinct roles for cyclin-dependent kinases in cell cycle control Science 1993, 262, 2050-2054
8. Loyer, P.; Trembley, J. H.; Katona, R.; Kidd, V. J.; Lahti, J. M. Role of CDK/cyclin complexes in transcription and RNA splicing Cell. Signalling 2005, 17, 1033-1051
9. Zhao, J.; Kennedy, B. K.; Lawrence, B. D.; Barbie, D. A.; Gregory Matera, A.; Fletcher, J. A.; Harlow, E. NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription Genes Dev. 2000, 14, 2283-2297
10. Malumbres, M.; Barbacid, M. To cycle or not to cycle: a critical decision in cancer Nat. Rev. Cancer 2001, 1, 222-231
11. Porter, P. L.; Malone, K. E.; Heagerty, P. J.; Alexander, G. M.; Gatti, L. A.; Firpo, E. J.; Daling, J. R.; Roberts, J. M. Expression of cell-cycle regulators p27 (Kip1) and cyclin E, alone and in combination, correlate with survival in young breast cancer patients Nat. Med. 1997, 3, 222-225
12. Schraml, P.; Bucher, C.; Bissig, H.; Nocito, A.; Haas, P.; Wilber, K.; Seelig, S.; Kononen, J.; Mihatsch, M. J.; Dirnhofer, S.; Sauter, G. Cyclin E overexpression and amplification in human tumours J. Pathol. 2003, 200, 375-382
13. Soria, J. C.; Se JJ.; Khuri, F. R.; Hassan, K.; Liu, D.; Waun, Ki, H.; Mao, L. Overexpression of cyclin B1 in early-stage non-small cell lung cancer and its clinical implication Cancer Res. 2000, 60, 4000-4004
14. Takeno, S.; Noguchi, T.; Kikuchi, R.; Uchida, Y.; Yokoyama, S.; Muller, W. Prognostic value of cyclin B1 in patients with esophageal squamous cell carcinoma Cancer 2002, 94, 2874-2881 (Pubitemid 34547686)
15. Tetsu, O.; McCormick, F. Proliferation of cancer cells despite CDK2 inhibition Cancer Cell 2003, 3, 233-245
16. Du, J.; Widlund, H. R.; Horstmann, M. A.; Ramaswamy, S.; Ross, K.; Huber, W. E.; Nishimura, E. K.; Golub, T. R.; Fisher, D. E. Critical role of CDK2 for melanoma growth linked to its melanocyte-specific transcriptional regulation by MITF Cancer Cell 2004, 6, 565-576
17. Hanse, E. A.; Nelsen, C. J.; GoggM. M.; Anttila, C. K.; Mullany, L. K.; Berthet, C.; Kaldis, P.; Crary, G. S.; Kuriyama, R.; Albrecht, J. H. Cdk2 plays a critical role in hepatocyte cell cycle progression and survival in the setting of cyclin D1 expression in vivo Cell Cycle 2009, 8, 2802-2809
18. Cai, D.; Latham, V. M., Jr.; Zhang, X.; Shapiro, G. I. Combined depletion of cell cycle and transcriptional cyclin-dependent kinase activities induces apoptosis in cancer cells Cancer Res. 2006, 66, 9270-9280
19. Fischer, P. M.; Gianella-Borradori, A. Recent progress in the discovery and development of cyclin-dependent kinase inhibitors Expert Opin. Invest. Drugs 2005, 14, 457-477
20. McClue, S. J.; Blake, D.; Clarke, R.; Cowan, A.; Cummings, L.; Fischer, P. M.; MacKenzie, M.; Melville, J.; Stewart, K.; Wang, S.; Zhelev, N.; Zheleva, D.; Lane, D. P. In vitro and in vivo antitumor properties of the cyclin dependent kinase inhibitor CYC202 (R-roscovitine) In. J. Cancer 2002, 102, 463-468
21. Misra, R. N.; Xiao, H. Y.; Kim, K. S.; Lu, S.; Han, W. C.; Barbosa, S. A.; Hunt, J. T.; Rawlins, D. B.; Shan, W.; Ahmed, S. Z.; Qian, L.; Chen, B. C.; Zhao, R.; Bednarz, M. S.; Kellar, K. A.; Mulheron, J. G.; Batorsky, R.; Roongta, U.; Kamath, A.; Marathe, P.; Ranadive, S. A.; Sack, J. S.; Tokarski, J. S.; Pavletich, N. P.; Lee, F. Y. F.; Webster, K. R.; Kimball, S. D. N -(Cycloalkylamino)acyl-2-aminothiazole Inhibitors of Cyclin-Dependent Kinase 2. N -[5-[[[5-(1,1-Dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4- piperidinecarboxamide (BMS-387032), a Highly Efficacious and Selective Antitumor Agent J. Med. Chem. 2004, 47, 1719-1728
22. Toogood, P. L.; Harvey, P. J.; Repine, J. T.; Sheehan, D. J.; VanderWel, S. N.; Zhou, H.; Keller, P. R.; McNamara, D. J.; Sherry, D.; Zhu, T.; Brodfuehrer, J.; Choi, C.; Barvian, M. R.; Fry, D. W. Discovery of a potent and selective inhibitor of cyclin-dependent kinase 4/6 J. Med. Chem. 2005, 48, 2388-2406
23. Moon, M. J.; Lee, S. K.; Lee, J. W.; Song, W. K.; Kim, S. W.; Kim, J. I.; Cho, C.; Choi, S. J.; Kim, Y. C. Synthesis and Structure-activity relationships of novel indirubin derivatives as potent antiproliferative agents with CDK2 inhibitory activities Bioorg. Med. Chem. 2006, 14, 237-246
24. Myrianthopoulos, V.; Magiatis, P.; FerandY.; Skaltsounis, A. L.; Meijer, L.; Mikros, E. An integrated computational approach to the phenomenon of potent and selective inhibition of aurora kinases B and C by a series of 7-substituted indirubins J. Med. Chem. 2007, 50, 4027-4037
25. Vougogiannopoulou, K.; FerandY.; Bettayeb, K.; Myrianthopoulos, V.; Lozach, O.; Fan, Y.; Johnson, C. H.; Magiatis, P.; Skaltsounis, A. L.; Mikros, E.; Meijer, L. Soluble 3′,6-substituted indirubins with enhanced selectivity toward glycogen synthase kinase -3 alter circadian period J. Med. Chem. 2008, 51, 6421-6431
26. Beauchard, A.; Laborie, H.; Rouillard, H.; Lozach, O.; FerandY.; Guevel, R. L.; Guguen-Guillouzo, C.; Meijer, L.; Besson, T.; Thiery, V. Synthesis and kinase inhibitory activity of novel substituted indigoids Bioorg. Med. Chem. 2009, 17, 6257-6263
27. Lee, M. J.; Kim, M. Y.; Mo, J. S.; Ann, E. J.; Seo, M. S.; Hong, J. A.; Kim, Y. C.; Park, H. S. Indirubin-3′-monoxime, a derivative of a Chinese anti-leukemia medicine, inhibits Notch1 signaling Cancer Lett. 2008, 265, 215-225
28. Yoon, J. H.; Kim, S. A.; Kwon, S. M.; Park, J. H.; Park, H. S.; Kim, Y. C.; Yoon, J. H.; Ahn, S. G. 5′-Nitro-indirubinoxime induces G1 cell cycle arrest and apoptosis in salivary gland adenocarcinoma cells through the inhibition of Notch-1 signaling Biochim. Biophys. Acta 2010, 1800, 352-358
29. Park, E. J.; Choi, S. J.; Kim, Y. C.; Lee, S. H.; Park, S. W.; Lee, S. K. Novel small molecule activators of β-catenin-mediated signaling pathway: Structure-activity relationships of indirubins Bioorg. Med. Chem. Lett. 2009, 19, 2282-2284
30. 3- and all- trans retinoic acid-induced differentiation of HL-60 leukemia cells Bioorg. Med. Chem. 2006, 14, 6752-6758
31. Jautelat, R.; Brumby, T.; Schafer, M.; Briem, H.; Eisenbrand, G.; Schwahn, S.; Kruger, M.; Lucking, U.; Prien, O.; Siemeister, G. From the insoluble dye indirubin towards highly active, soluble CDK2-inhibitors ChemBioChem 2005, 6, 531-540
32. Helen, C. F.; Su; Tsou, K. C. Synthesis of bromo-substituted indoxyl esters for cytochemical demonstration of enzyme activity Cytochem. Demon. Enzyme Act. 1960, 82, 1187-1189
33. Woodhead, A. J.; Berdini, V.; Boulstridge, J. A.; Carr, M. G.; Cross, D. M.; Davis, D. J.; Devine, L. A.; Early, T. R.; Feltell, R. E.; Lewis, E. J.; McMenamR. L.; Navarro, E. F.; O'Brien, M. A.; O'Reilly, M.; Reule, M.; Saxty, G.; Seavers, L. C. A.; Smith, D.-M.; Squires, M. S.; Trewartha, G.; Walker, M. T.; Woolford, A. J. A. Identification of N -(4-Piperidinyl)-4-(2,6- dichlorobenzoylamino)-1 H -pyrazole-3-carboxamide (AT7519), a Novel Cyclin Dependent Kinase Inhibitor Using Fragment-Based X-Ray Crystallography and Structure Based Drug Design J. Med. Chem. 2008, 51, 4986-4999
34. Beauchard, A.; FerandY.; Frere, S.; Lozach, O.; Blairvacq, M.; Meijer, L.; Thiery, V.; Besson, T. Synthesis of novel 5-substituted indirubins as protein kinases inhibitors Bioorg. Med. Chem. 2006, 14, 6434-6443
35. Shtutman, M.; Zhurinsky, J.; Simcha, I.; Albanese, C.; D'Amico, M.; Pestell, R.; Ben-Ze'ev, A. The cyclin D1 gene is a target of the β-catenin/LEF-1 pathway Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 5522-5527
36. Kim, S.-A.; Kim, Y.-C.; Kim, S.-W.; Lee, S.-H.; MJ.-J.; Ahn, S.-G.; Yoon, J.-H. Antitumor Activity of Novel Indirubin Derivatives in Rat Tumor Model Clin. Cancer Res. 2007, 13, 253-259
37. Nam, S.; Buettner, R.; Turkson, J.; Kim, D.; Cheng, J. Q.; Muehlbeyer, S.; Hippe, F.; Vatter, S.; Merz, K. H.; Eisenbrand, G.; Jove, R. Indirubin derivatives inhibit Stat3 signaling and induce apoptosis in human cancer cells Proc. Nat. Acad. Sci. U.S.A. 2005, 102, 5998-6003
38. Kim, S. A.; Kim, S. W.; Chang, S.; Yoon, J. H.; Ahn, S. G. 5′-Nitro-indirubinoxime induces G2/M cell cycle arrest and apoptosis in human KB oral carcinoma cells Cancer Lett. 2009, 274, 72-77
39. BaJ.; Mclauchlan, H.; Elliott, M.; Cohen, P. The specificities of protein kinase inhibitors: an update Biochem. J. 2003, 371, 199-204
40. Pan, W.; Liu, H.; Xu, Y. J.; Chen, X.; Kim, K. H.; Milligan, D. L.; Columbus, J.; Hadari, Y. R.; Kussie, P.; Wong, W. C.; Labelle, M. Pyrimido-oxazepine as a versatile template for the development of inhibitors of specific kinases Bioorg. Med. Chem. Lett. 2005, 15, 5474-5477
41. Skehan, P.; Storeng, R.; Scudiero, D.; Monks, A.; McMahon, J.; Vistica, D.; Warren, J. T.; Bokesch, H.; Kenney, S.; Boyd, M. R. New colorimetric cytotoxicity assay for anticancer drug screening J. Natl. Cancer Inst. 1990, 82, 1107-1112