Synthesis and evaluation of indole-based chalcones as inducers of methuosis, a novel type of nonapoptotic cell death

Journal of Medicinal Chemistry

Volumn 55, Issue 5, 2012, Pages 1940-1956

  Robinson, Michael W ^a   Overmeyer, Jean H ^a   Young, Ashley M ^a   Erhardt, Paul W ^a   Maltese, William A ^a  

^a MEDICAL COLLEGE OF OHIO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 METHYL 1H INDOL 5 OL; 2 METHYL 5 BENZOYL INDOLE 3 CARBOXALDEHYDE; 2 METHYL 6 BENZOYL INDOLE 3 CARBOXALDEHYDE; 2 METHYLINDOLE 3 CARBOXALDEHYDE; 3 (2 METHYL 1H INDOL 3 YL) 1 (4 PYRIDINYL) 2 PROPEN 1 ONE; 3 (5 METHOXY, 2 METHYL 1H INDOL 3 YL) 1 (4 PYRIDINYL) 2 PROPEN 1 ONE; 5 (4 BENZOATE)METHOXY 2 METHYL 1H INDOLE 3 CARBOXALDEHYDE; 5 (4 METHYLBENZOATE)METHOXY 2 METHYL 1H INDOLE; 5 (4 METHYLBENZOATE)METHOXY 2 METHYL 1H INDOLE 3 CARBOXALDEHYDE; 5 METHOXY 2 METHYL 1H INDOLE 3 CARBOXALDEHYDE; ANTINEOPLASTIC AGENT; CHALCONE; DOXORUBICIN; TEMOZOLOMIDE; TRANS 3 (1H INDOL 3 YL) 1 (2 PYRIDINYL) 2 PROPEN 1 ONE; TRANS 3 (1H INDOL 3 YL) 1 (3 PYRIDINYL) 2 PROPEN 1 ONE; TRANS 3 (1H INDOL 3 YL) 1 (4 PYRIDINYL) 2 PROPEN 1 ONE; TRANS 3 (1H INDOL 3 YL) 1 PHENYL 2 PROPEN 1 ONE; TRANS 3 (2 METHYL 1H INDOL 3 YL) 1 (4 PYRIDINYL) 2 PROPEN 1 ONE; TRANS 3 (5 HYDROXY 1H INDOL 3 YL) 1 (4 PYRIDINYL) 2 PROPEN 1 ONE; TRANS 3 (5 METHOXY 1 METHYL INDOL 3 YL) 1 (4 PYRIDINYL) 2 PROPEN 1 ONE; TRANS 3 (5 METHOXY 1H INDOL 3 YL) 1 (3 PYRIDINYL) 2 PROPEN 1 ONE; TRANS 3 (5 METHOXY 1H INDOL 3 YL) 1 (4 PYRIDINYL) 2 PROPEN 1 ONE; TRANS 3 (5 METHOXY 1H INDOL 3 YL) 1 (PYRAZINE) 2 PROPEN 1 ONE; TRANS 3 (5 METHOXY 2 METHYL 1H INDOL 3 YL) 1 (4 PYRIDINYL) 2 PROPEN 1 ONE; TRANS 3 (5 PHENYLMETHOXY 1H INDOL 3 YL) 1 (4 PYRIDINYL) 2 PROPEN 1 ONE; TRANS 3 (6 BENZOYL 2 METHYL 1H INDOL 3 YL) 1 (4 PYRIDINYL) 2 PROPEN 1 ONE; TRANS 3 [5 [(4 CARBOXYPHENYL) METHOXY] 1H INDOL 3 YL]]] 1 (4 PYRPYRIDINYL) 2 PROPEN 1 ONE; TRANS 3 [5 [(4 METHYLBENZOATE)METHOXY] 1H INDOL 3 YL]] 1 (4 PYRIDINYL) 2 PROPEN 1 ONE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ARTICLE; BREAST CANCER; CANCER CELL; CANCER GROWTH; CELL DEATH; CONTROLLED STUDY; DRUG SYNTHESIS; GLIOBLASTOMA; HUMAN; HUMAN CELL; PHOTOAFFINITY LABELING; PROTEIN TARGETING; STRUCTURE ACTIVITY RELATION;

ANTINEOPLASTIC AGENTS; AZIDES; CELL DEATH; CELL LINE, TUMOR; CELL SURVIVAL; CHALCONES; DRUG RESISTANCE, NEOPLASM; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; INDOLES; PHOTOAFFINITY LABELS; PYRIDINES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84858032579     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm201006x     Document Type: Article

References (58)

1. Stupp, R.; Mason, W. P.; van den Bent, M. J.; Weller, M.; Fisher, B.; Taphoorn, M. J.; Belanger, K.; Brandes, A. A.; Marosi, C.; Bogdahn, U.; Curschmann, J.; Janzer, R. C.; Ludwin, S. K.; Gorlia, T.; Allgeier, A.; Lacombe, D.; Cairncross, J. G.; Eisenhauer, E.; Mirimanoff, R. O. Radiotherapy plus concomitant and adjuvant Temozolomide for glioblastoma N. Engl. J. Med. 2005, 352, 987-996
2. Norbury, C. J.; Zhivotovsky, B. DNA damage-induced apoptosis Oncogene 2004, 23, 2797-2808
3. Ishii, N.; Maier, D.; Merlo, A.; Tada, M.; Sawamura, Y.; Diserens, A.-C.; Van Meir, E. G. Frequnt co-alterations of TP53, p16/CDKN2A, p14arf, PTEN tumor suppressor genes in human glioma cell lines Brain Pathol. 1999, 9, 469-479
4. Furnari, F. B.; Fenton, T.; Bachoo, R. M.; Mukasa, A.; Stommel, J. M.; Stegh, A.; Hahn, W. C.; Ligon, K. L.; Louis, D. N.; Brennan, C.; Chin, L.; DePinho, R. A.; Cavenee, W. K. Malignant astrocytic glioma: Genetics, biology, and paths to treatment Genes Dev. 2007, 21, 2683-2710
5. Bocangel, D. B.; Finkelstein, S.; Schold, S. C.; Bhakat, K. K.; Mitra, S.; Kokkinakis, D. M. Multifaceted resistance of gliomas to Temozolomide Clin. Cancer Res. 2002, 8, 2725-2734
6. Overmeyer, J. H.; Kaul, A.; Johnson, E. E.; Maltese, W. A. Active ras triggers death in glioblastoma cells through hyperstimulation of macropinocytosis Mol. Cancer Res 2008, 6, 965-977
7. Bhanot, H.; Young, A. M.; Overmeyer, J. H.; Maltese, W. A. Induction of non-apoptotic cell death by activated Ras requires inverse regulation of Rac1 and Arf6 Mol. Cancer Res. 2010, 8, 1358-1374
8. Swanson, J. A.; Watts, C. Macropinocytosis Trends Cell Biol. 1995, 5, 424-428
9. Donaldson, J. G.; Porat-Shliom, N.; Cohen, L. A. Clathrin-independent endocytosis: A unique platform for cell signaling and PM remodeling Cell Signalling 2009, 21, 1-6
10. Overmeyer, J. H.; Young, A. M.; Bhanot, H.; Maltese, W. A. A Chalcone-Related Small Molecule That Induces Methuosis, a Novel Form of Non-Apoptotic Cell Death, in Glioblastoma Cells Mol. Cancer 2011, 10, 69
11. Cerny, J.; Feng, Y.; Yu, A.; Miyake, K.; Borgonovo, B.; Klumperman, J.; Meldolesi, J.; McNeil, P. L.; Kirchhausen, T. The small chemical vacuolin-1 inhibits Ca(2+)-dependent lysosomal exocytosis but not cell resealing EMBO Rep. 2004, 5, 883-888
12. Go, M. L.; Wu, X.; Liu, X. L. Chalcones: An update on cytotoxic and chemoprotective properties Curr. Med. Chem. 2005, 12, 481-499
13. Kamal, A.; Ramakrishna, G.; Raju, P.; Viswanath, A.; Ramaiah, M. J.; Balakishan, G.; Pal-Bhadra, M. Synthesis and anti-cancer activity of chalcone linked imidazolones Bioorg. Med. Chem. Lett. 2010, 20, 4865-4869
14. Kumar, D.; Kumar, N. M.; Akamatsu, K.; Kusaka, E.; Harada, H.; Ito, T. Synthesis and biological evaluation of indolyl chalcones as antitumor agents Bioorg. Med. Chem. Lett. 2010, 20, 3916-3919
15. Lindwall, H. G.; Order, R. B. V. 3-Indole aldehyde and certain of its condensation products J. Org. Chem. 1945, 10, 128-133
16. Pasquini, S.; Mugnaini, C.; Brizzi, A.; Ligresti, A.; Di, M., V; Ghiron, C.; Corelli, F. Rapid combinatorial access to a library of 1,5-disubstituted-3- indole-N-alkylacetamides as CB2 receptor ligands J. Comb. Chem. 2009, 11, 795-798
17. Lomenick, B.; Olsen, R. W.; Huang, J. Identification of direct protein targets of small molecules ACS Chem. Biol. 2011, 6, 34-46
18. Hatanaka, Y.; Sadakane, Y. Photoaffinity labeling in drug discovery and developments: chemical gateway for entering proteomic frontier Curr. Top. Med. Chem. 2002, 2, 271-288
19. Galardy, R. E.; Craig, L. C.; Printz, M. P. Benzophenone triplet: A new photochemical probe of biological ligand-receptor interactions Nat. New Biol. 1973, 242, 127-128
20. Liu, D.; O'Leary, B.; Iruthayanathan, M.; Love-Homan, L.; Perez-Hernandez, N.; Olivo, H. F.; Dillon, J. S. Evaluation of a novel photoactive and biotinylated dehydroepiandrosterone analog Mol. Cell. Endocrinol. 2010, 328, 56-62
21. Hasegawa, M.; Miura, T.; Kuzuya, K.; Inoue, A.; Won, K. S.; Horinouchi, S.; Yoshida, T.; Kunoh, T.; Koseki, K.; Mino, K.; Sasaki, R.; Yoshida, M.; Mizukami, T. Identification of SAP155 as the target of GEX1A (Herboxidiene), an antitumor natural product ACS Chem. Biol. 2011, 6, 229-233
22. Demopoulos, V. J.; Nicolaou, I. Electrophilic substitution of indole on the benzene moiety: A synthesis of 5-acyl- and 5-aroylindoles Synthesis 1998, 1998, 1519-1522
23. Miller, D. K.; Gillard, J. W.; Vickers, P. J.; Sadowski, S.; Leveille, C.; Mancini, J. A.; Charleson, P.; Dixon, R. A.; Ford-Hutchinson, A. W.; Fortin, R. Identification and isolation of a membrane protein necessary for leukotriene production Nature 1990, 343, 278-281
24. Palnitkar, S. S.; Bin, B.; Jimenez, L. S.; Morimoto, H.; Williams, P. G.; Paul-Pletzer, K.; Parness, J. [3H]Azidodantrolene: Synthesis and use in identification of a putative skeletal muscle dantrolene binding site in sarcoplasmic reticulum J. Med. Chem. 1999, 42, 1872-1880
25. He, G.; Luo, W.; Li, P.; Remmers, C.; Netzer, W. J.; Hendrick, J.; Bettayeb, K.; Flajolet, M.; Gorelick, F.; Wennogle, L. P.; Greengard, P. Gamma-secretase activating protein is a therapeutic target for Alzheimer's disease Nature 2010, 467, 95-98
26. Noland, W. E.; Smith, L. R.; Johnson, D. C. Nitration of indoles: II.The mononitration of methylindoles J. Org. Chem. 1963, 28, 2262-2266
27. Melhado, L. L.; Leonard, N. J. An efficient synthesis of azidoindoles and azidotryptophans J. Org. Chem. 1983, 48, 5130-5133
28. Uetrecht, J. Idiosyncratic drug reactions: current understanding Annu. Rev. Pharmacol. Toxicol. 2007, 47, 513-539
29. Raja, S. M.; Clubb, R. J.; Ortega-Cava, C.; Williams, S. H.; Bailey, T. A.; Duan, L.; Zhao, X.; Reddi, A. L.; Nyong, A. M.; Natarajan, A.; Band, V.; Band, H. Anticancer activity of Celastrol in combination with ErbB2-targeted therapeutics for treatment of ErbB2-overexpressing breast cancers Cancer Biol. Ther. 2011, 11, 263-276
30. Macpherson, L. J.; Dubin, A. E.; Evans, M. J.; Marr, F.; Schultz, P. G.; Cravatt, B. F.; Patapoutian, A. Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines Nature 2007, 445, 541-545
31. Yamakoshi, H.; Kanoh, N.; Kudo, C.; Sato, A.; Ueda, K.; Muroi, M.; Kon, S.; Satake, M.; Ohori, H.; Ishioka, C.; Oshima, Y.; Osada, H.; Chiba, N.; Shibata, H.; Iwabuchi, Y. KSRP/FUBP2 is a binding protein of GO-YO86, a cytotoxic curcumin analogue ACS Med. Chem. Lett. 2010, 1, 273-276
32. Maresso, A. W.; Wu, R.; Kern, J. W.; Zhang, R.; Janik, D.; Missiakas, D. M.; Duban, M. E.; Joachimiak, A.; Schneewind, O. Activation of inhibitors by sortase triggers irreversible modification of the active site J. Biol. Chem. 2007, 282, 23129-23139
33. Singh, J.; Petter, R. C.; Baillie, T. A.; Whitty, A. The resurgence of covalent drugs Nat. Rev. Drug Discovery 2011, 10, 307-317
34. Stoll, R.; Renner, C.; Hansen, S.; Palme, S.; Klein, C.; Belling, A.; Zeslawski, W.; Kamionka, M.; Rehm, T.; Muhlhahn, P.; Schumacher, R.; Hesse, F.; Kaluza, B.; Voelter, W.; Engh, R. A.; Holak, T. A. Chalcone derivatives antagonize interactions between the human oncoprotein MDM2 and p53 Biochemistry 2001, 40, 336-344
35. Bois, F.; Boumendjel, A.; Mariotte, A. M.; Conseil, G.; Di Petro, A. Synthesis and biological activity of 4-alkoxy chalcones: potential hydrophobic modulators of P-glycoprotein-mediated multidrug resistance Bioorg. Med. Chem. 1999, 7, 2691-2695
36. Hadjeri, M.; Barbier, M.; Ronot, X.; Mariotte, A. M.; Boumendjel, A.; Boutonnat, J. Modulation of P-glycoprotein-mediated multidrug resistance by flavonoid derivatives and analogues J. Med. Chem. 2003, 46, 2125-2131
37. Liu, X. L.; Tee, H. W.; Go, M. L. Functionalized chalcones as selective inhibitors of P-glycoprotein and breast cancer resistance protein Bioorg. Med. Chem. 2008, 16, 171-180
38. Edwards, M. L.; Stemerick, D. M.; Sunkara, P. S. Chalcones: A new class of antimitotic agents J. Med. Chem. 1990, 33, 1948-1954
39. Dupeyre, G.; Chabot, G. G.; Thoret, S.; Cachet, X.; Seguin, J.; Guenard, D.; Tillequin, F.; Scherman, D.; Koch, M.; Michel, S. Synthesis and biological evaluation of (3,4,5-trimethoxyphenyl)indol-3-ylmethane derivatives as potential antivascular agents Bioorg. Med. Chem. 2006, 14, 4410-4426
40. Boumendjel, A.; McLeer-Florin, A.; Champelovier, P.; Allegro, D.; Muhammad, D.; Souard, F.; Derouazi, M.; Peyrot, V.; Toussaint, B.; Boutonnat, J. A novel chalcone derivative which acts as a microtubule depolymerising agent and an inhibitor of P-gp and BCRP in in-vitro and in-vivo glioblastoma models BMC Cancer 2009, 9, 242
41. Boumendjel, A.; Ronot, X.; Boutonnat, J. Chalcones derivatives acting as cell cycle blockers: potential anti cancer drugs? Curr. Drug Targets 2009, 10, 363-371
42. Ducki, S. Antimitotic chalcones and related compounds as inhibitors of tubulin assembly Anticancer Agents Med. Chem. 2009, 9, 336-347
43. Champelovier, P.; Mininno, M.; Duchamp, E.; Nicolle, E.; Curri, V.; Boumendjel, A.; Boutonnat, J. Cytotoxicity of chalcone derivatives towards glioblastoma Anticancer Res. 2011, 31, 3213-3218
44. Chao, T. C.; Chu, Z.; Tseng, L. M.; Chiou, T. J.; Hsieh, R. K.; Wang, W. S.; Yen, C. C.; Yang, M. H.; Hsiao, L. T.; Liu, J. H.; Chen, P. M. Paclitaxel in a novel formulation containing less Cremophor EL as first-line therapy for advanced breast cancer: A phase II trial Invest. New Drugs 2005, 23, 171-177
45. McCarron, P. A.; Marouf, W. M.; Quinn, D. J.; Fay, F.; Burden, R. E.; Olwill, S. A.; Scott, C. J. Antibody targeting of camptothecin-loaded PLGA nanoparticles to tumor cells Bioconjugate Chem. 2008, 19, 1561-1569
46. Danhier, F.; Lecouturier, N.; Vroman, B.; Jerome, C.; Marchand-Brynaert, J.; Feron, O.; Preat, V. Paclitaxel-loaded PEGylated PLGA-based nanoparticles: in vitro and in vivo evaluation J. Controlled Release 2009, 133, 11-17
47. Emerson, D. L. Liposomal delivery of camptothecins Pharm. Sci. Technol. Today 2000, 3, 205-209
48. Yang, T.; Cui, F. D.; Choi, M. K.; Lin, H.; Chung, S. J.; Shim, C. K.; Kim, D. D. Liposome formulation of paclitaxel with enhanced solubility and stability Drug Delivery 2007, 14, 301-308
49. Park, Y. S. Tumor-directed targeting of liposomes Biosci. Rep. 2002, 22, 267-281
50. Ruoslahti, E.; Bhatia, S. N.; Sailor, M. J. Targeting of drugs and nanoparticles to tumors J. Cell Biol. 2010, 188, 759-768
51. Dolby, L. J.; Rodia, R. M. The periodate oxidation of heterocycles: II. 2-Methylindole and 2,3-diphenylindole J. Org. Chem. 1970, 35, 1493-1496
52. Note that although no published analytical data were found, the following compounds have CAS numbers: compound 2, 373618-91-8; compound 10, 1237055-51-4; 2012.
53. Tsukerman, S. V.; Nikitchenko, V. M.; Bugai, A. I.; Lavrishin, V. F. Synthesis of analogs of chalcones and derivatives of delta 2-pyrazoline based on 3-formylindole Khimiia Geterotsiklicheskikh Soedinenii 1969, 2, 268-272
54. Gillard, J. W.; Belanger, P. Metabolic synthesis of arylacetic acid antiinflammatory drugs from arylhexenoic acids. 2. Indomethacin J. Med. Chem. 1987, 30, 2051-2058
55. Beer, R. J. S.; Clarke, K.; Davenport, H. F.; Robertson, A. The chemistry of the melanins. III/. The synthesis of hydroxyindoles from p-benzoquinones J. Chem. Soc. 1951, 2029-2032
56. Guo, B.; Hembruff, S. L.; Villeneuve, D. J.; Kirwan, A. F.; Parissenti, A. M. Potent killing of paclitaxel- and doxorubicin-resistant breast cancer cells by calphostin C accompanied by cytoplasmic vacuolization Breast Cancer Res Treat. 2003, 82, 125-141
57. Maltese, W. A.; De Vivo, D. C. Cholesterol and phospholipids in cultured skin fibroblasts from patients with dystonia Ann. Neurol. 1984, 16, 250-252
58. Garbe, J. C.; Bhattacharya, S.; Merchant, B.; Bassett, E.; Swisshelm, K.; Feiler, H. S.; Wyrobek, A. J.; Stampfer, M. R. Molecular distinctions between stasis and telomere attrition senescence barriers shown by long-term culture of normal human mammary epithelial cells Cancer Res. 2009, 69, 7557-7568