Synthesis and in vitro and in vivo antitumor activity of 2-phenylpyrroloquinolin-4-ones

Journal of Medicinal Chemistry

Volumn 48, Issue 9, 2005, Pages 3417-3427

  Ferlin, Maria Grazia ^a   Chiarelotto, Gianfranco ^a   Gasparotto, Venusia ^a   Dalla Via, Lisa ^a   Pezzi, Vincenzo ^b   Barzon, Luisa ^a   Palu, Giorgio ^a   Castagliuolo, Ignazio ^a  

^a UNIVERSITY OF PADOVA   (Italy)

^b UNIVERSITY OF CALABRIA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

1H,7H PYRROLO[2,3 H]QUINOLIN 4 ONE; 2 (3 AMINOPHENYL) 1H,7H PYRROLO[2,3 H]QUINOLIN 4 ONE; 2 (3 METHOXYPHENYL) 1H,7H PYRROLO[2,3 H]QUINOLIN 4 ONE; 2 (3 NITROPHENYL) 1H,7H PYRROLO[2,3 H]QUINOLIN 4 ONE; 2 (4 NITROPHENYL) 1H,7H PYRROLO[2,3 H]QUINOLIN 4 ONE; 2 METHYL 1H,7H PYRROLO[2,3 H]QUINOLIN 4 ONE; 2 PHENYL 1H,7H PYRROLO[2,3 H]QUINOLIN 4 ONE; 2 PHENYL N7 METHYL 1H PYRROLO[2,3 H]QUINOLIN 4 ONE; 2 PHENYLPYRROLOQUINOLIN 4 ONE DERIVATIVE; 2 THIENYL 1H,7H PYRROLO[2,3 H]QUINOLIN 4 ONE; QUINOLINE DERIVATIVE; UNCLASSIFIED DRUG; VINCRISTINE;

ADENOCARCINOMA; ADRENAL CORTEX CARCINOMA; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; BREAST CANCER; CANCER INHIBITION; CELL CYCLE; CELL CYCLE G2 PHASE; CHROMATOPHORE; CONTROLLED STUDY; CYTOTOXICITY; DRUG STRUCTURE; DRUG SYNTHESIS; HORMONE SENSITIVITY; HUMAN; HUMAN CELL; IC 50; IN VIVO STUDY; LIVER CANCER; LIVER CELL CARCINOMA; MICROTUBULE ASSEMBLY; MITOSIS INHIBITION; MOUSE; NONHUMAN; OVARY CANCER; STRUCTURE ACTIVITY RELATION; TUMOR CELL LINE;

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; AROMATASE INHIBITORS; CARCINOMA, HEPATOCELLULAR; CELL CYCLE; CELL LINE, TUMOR; DNA TOPOISOMERASES, TYPE I; DNA TOPOISOMERASES, TYPE II; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; LIVER NEOPLASMS; MALE; MICE; MICE, INBRED BALB C; MICROTUBULES; NEOPLASM TRANSPLANTATION; NEOPLASMS, HORMONE-DEPENDENT; PYRROLES; QUINOLINES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 18244400107     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm049387x     Document Type: Article

References (52)

1. Jordan, M. A.; Wilson, L. Microtubules as a target for anticancer drugs. Nat. Rev. 2004, 4, 253-64.
2. Xia, Y.; Yang, Z. Y.; Xia, P.; Bastow, K. F.; Tachibana, Y.; Kuo, S. C.; Hamel, E.; Hackl, T.; Lee, K. H. Antitumor Agents. 181. Synthesis and biological evaluation of 6,7,2′,3′,4′-substituted-1,2,3,4-tetrahydro-2- phenyl-4-quinolones as a new class of antimitotic antitumor agents. J. Med. Chem. 1998, 41, 1155-62.
3. Lee, K. H.; Tagahara, K.; Suzuki, H.; Wu, R. Y.; Haruna, M.; Hall, I. H.; Huang, H. C.; Ito, K.; Iida, T.; Lai, J. S. Antitumor agents. 49 Tricin, Kaempferol-3-O-β-D-glucopyranoside and (+)-nortrachelogenin, antileukemic principles from Wikstroemia indica. J. Nat. Prod. 1981, 44 (5), 530-5.
4. Shi, Q.; Chen, K.; Li, L. Antitumor Agents. 154. Cytotoxic and antimitotic flavonols from Polanisia dodecandra. J. Nat. Prod. 1995, 58, 475-82.
5. Manthey, J. A.; Guthrie, N.; Grohmann, K. Biological properties of citrus flavonoids pertaining to cancer and inflammation. Curr. Med. Chem. 2001, 8, 135-53.
6. Hodek, P.; Trefil, P.; Stiborova, M. Flavonoid-potent and versatile biologically active compounds interacting with cytochromes P450. Chem. Biol. Interact. 2002, 139, 1-21.
7. Manthey, J. A.; Guthrie, N. Antiproliferative activities of citrus flavonoids against six human cancer cell lines. J. Agric. Food Chem. 2002, 50, 5837-43.
8. Lin, J. H.; Lu, A. Y. H. Inhibition and induction of cytochrome P450 and the clinical implications. Clin. Pharmacokinet. 1998, 35, 361-90.
9. Yin, F.; Giuliano, A. E.; Van Herle, A. J. Signal pathways involved in apigenin inhibition of growth and induction of apoptosis of human anaplastic thyroid cancer cells (ARO). Anticancer Res. 1999, 19, 4297-303.
10. Constantinou, A.; Mehta, R.; Runyan, C.; Rao, K.; Vaughan, R. M. Flavonoids as DNA topoisomerase antagonists and poisons: structure-activity relationship. J. Nat. Prod. 1995, 58, 217-25.
11. Pouget, C.; Fagnere, C.; Basly, J. P.; Besson, A. E.; Champavier, Y.; Habrioux, G.; Chulia, A. J. Synthesis and aromatase inhibitory activity of flavones. Pharm. Res. 2002, 19 (3), 286-91.
12. Lee, D.; Bhat, K.; Fong, H.; Farnsworth, N.; Pezzuto, J.; Kinghorn, D. Aromatase inhibitors from Broussonetia papyrifera. J. Nat. Prod. 2001, 64, 1286-93.
13. Jeong, H.-J.; Shin, Y. G. Inhibition of aromatase activity by flavonoids. Arch. Pharm. Res. 1999, 22, 309-12.
14. Le Bail, J. C.; Varnat, F.; Nicolas, J. C.; Habrioux, G. Estrogenic and antiproliferative activities on MCF-7 human breast cancer cells by flavonoids. Cancer Lett. 1998, 130, 209-16.
15. Guthrie, N.; Carrol, K. K. Inhibition of mammary cancer by citrus flavonoids. Adv. Exp. Med. Biol. 1998, 439, 227-36.
16. So, F.; Guthrie, N.; Chambers, A.; Carroll, K. Inhibition of proliferation of estrogen receptor-positive MCF-7 human breast cancer cells by flavonoids in the presence and absence of excess estrogen. Cancer Lett. 1997, 112, 127-33.
17. Li, L.; Wang, H. K.; Kuo, S. C.; Wu, T. S.; Lednicer, D.; Lin, C. M.; Hamel, E.; Lee, K. H. Antitumor Agents. 150. 2′,3′,4′, 5′,5,6,7-Substituted 2-phenyl-4-quinolones and related compounds: their synthesis, cytotoxicity, and inhibition of tubulin polymerization. J. Med. Chem. 1994, 37, 1126-35.
18. Li, L.; Wang, H. K.; Kuo, S. C.; Wu, T. S.; Mauger, A.; Lin, C. M.; Hamel, E.; Lee, K. H. Antitumor agents. 155. Synthesis and biological evaluation of 3′,6,7-substituted 2-phenyl-4-quinolones as antimicrotubule agents. J. Med. Chem. 1994, 37, 3400-07.
19. Kuo, S. C.; Lee, H. Z.; Juang, J. P.; Lin, Y. T.; Wu, T. S.; Chang, J. J.; Lednicer, D.; Paull, K. D.; Lin, C. M.; Hamel, E.; Lee, K. H. Synthesis and cytotoxicity of 1,6,7,8-substituted 2-(4′-substituted phenyl)-4-quinolones and related compounds: identification as antimitotic agents interacting with tubulin. J. Med. Chem. 1993, 36, 1146-56.
20. Zhang, S. X.; Bastow, K. F.; Tachibana, Y.; Kuo, S. C.; Hamel, E.; Mauger, A.; Narayanan, V. L.; Lee, K. H. Antitumor Agents. 196. Substituted 2-thienyl-1,8-naphthyridin-4-ones: their synthesis, citotoxicity, and inhibition of tubulin polymerization. J. Med. Chem. 1999, 42, 4081-87.
21. Chen, K.; Kuo, S. C.; Hsieh, M. C.; Mauger, A.; Lin, C. M.; Hamel, E.; Lee, K. H. Antitumor Agents. 174. 2′,3′,4′,5,6,7-Substituted 2-phenyl-1,8-naphthyridin-4-ones: their synthesis, cytotoxicity, and inhibition of tubulin polymerization. J. Med. Chem. 1997, 40, 2266-75.
22. Chen, K.; Kuo, S. C.; Hsieh, M. C.; Mauger, A.; Lin, C. M.; Hamel, E.; Lee, K. H. Synthesis and biological evaluation of substituted 2-aryl-1,8-naphthyridin-4(1H)-ones as antitumor agents that inhibit tubulin polymerization. J. Med. Chem. 1997, 40, 3049-56.
23. Kasahara, A.; Izumi, A. New synthesis of 2-aryl-4-quinolones. Chem. Ind. (London) 1981, 4, 121.
24. Zhang, S. X.; Feng, J.; Kuo, S. C.; Brossi, A.; Hamel, E.; Tropsha, A.; Lee, K. H. Antitumor Agents. 199. Three-dimensional quantitative structure-activity relationship study of the colchicine binding site ligands using comparative molecular field analysis. J. Med. Chem. 2000, 43, 167-76.
25. Ferlin, M. G.; Gatto, B.; Chiarelotto, G.; Palumbo, M. Novel pyrrolo[3,2-f]quinolines: synthesis and antiproliferative activity. Bioorg. Med. Chem. 2001, 9, 1843-48.
26. Ferlin, M. G.; Gatto, B.; Chiarelotto, G.; Palumbo, M. Pyrroloquinoline derivatives as potent antineoplastic drugs. Bioorg. Med. Chem. 2000, 8, 1415-22.
27. Conrad, M.; Limpach, L. Ber. 1887, 20, 944-8; 1891, 24, 2990.
28. Conrad, M.; Limpach, L. Ber. 1887, 20, 944-8; 1891, 24, 2990.
29. Somei, M.; Inoue, S.; Tokutake, S.; Yamada, F.; Kaneko, C. The Chemistry of indoles. XIII. Syntheses of substituted indoles carrying an amino, nitro, methoxycarbonyl, or benzyloxy group at 4-position and their 1-hydroxy derivatives. Chem. Pharm. Bull. 1981, 29 (3), 726-38.
30. Batcho, A. D.; Leimgruber, W. Org. Synth. 1985, 63, 214.
31. Bergman, J.; Sand, P. 4-Nitroindole. Org. Synth. 1987, 65, 146-49.
32. Bergman, J.; Sand, P.; Tilstam, U. A new versatile synthesis of 4-nitroindoles. Tetrahedron Lett. 1983, 24, 3665-8.
33. Kikugawa, Y.; Miyake, Y. A Simple synthesis of N-alkylindoles. Synthesis 1981, 6, 461-2.
34. 1C receptor antagonist. J. Med. Chem. 1993, 38, 1104-7.
35. Bergman, J.; Sand, P. Synthesis of indoles via ring closure of 2-alkylnitroaniline Derivatives. Tetrahedron 1990, 46, 6085-6112.
36. Gould, R. G.; Jacobs, W. A. The synthesis of certain substituted quinolines and 5,6-benzoquinolines. J. Am. Chem. Soc. 1939, 61, 2890-5.
37. Wang, C. Z.; Maier, U. H.; Zenk, M. H. Synthesis of 3,3′,5- trihydroxybiphenyl-2-carboxylic acid, a component of the bitterest natural product amarogentin and its coenzyme A and N-acetyl cysteamine thiol esters. J. Nat. Prod. 2000, 63, 371-4.
38. 1 Synthesis of 1,3-dimethoxyfluoren-9-ones. Chem. Pharm. Bull. 1982, 30 (7), 2590-4.
39. Lawrence, N. J.; McGown, A. T.; Ducki, S.; Hadfield, J. A. The interaction of chalcones with tubulin. Anticancer Drug Des. 2000, 15, 135-141.
40. Pecere, T.; Gazzola, M. V.; Mucignat, C.; Parolin, C.; Dalla Vecchia, F.; Cavaggioni, A.; Basso, G.; Diaspro, A.; Salvato, B.; Carli, M.; Palù, G. Aloe-emodin is a new type of anticancer agent with selective activity against neuroectodermal tumors. Cancer Res. 2000, 60, 2800-04.
41. Chan, H. Y.; Wang, H.; Leung, L. K. The red clover (Trifolium pratense) isoflavone biochanin A modulates the biotransformation pathway of 7,12-dimethylbenz[a]anthracene. Br. J. Nutr. 2003, 90, 87-92.
42. Seralini, G.-E.; Moslemi, S. Aromatase inhibitors: past, present and future. Mol. Cell. Endocrinol. 2001, 117-31.
43. Lephart, E. D.; Simpson, E. R. Assay of aromatase activity. Methods Enzymol. 1991, 206, 477-83.
44. Tseng, L.; Malbon, C. C.; Lane, B. Kaplan, C.; Mazella, J.; Dahler, H.; Tseng, A. Progestin-dependent effect of forskolin on human endometrial aromatase activity. Hum. Reprod. 1987, 2, 371-77.
45. Buzdar, A. U. Pharmacology and pharmacokinetics of the newer generation aromatase inhibitors. Clin. Cancer Res. 2003, 9, 468-72.
46. Kao, Y.-C.; Zhou, C.; Sherman, M.; Laughton, C.; Chen, S. Molecular basis of the inhibition of human aromatase (estrogen synthetase) by flavone and isoflavone fhytoestrogens. A site-direct mutagenesis study. Environ. Health Perspect. 1998, 106, 85-92.
47. Recanatini, M.; Cavalli, A.; Valenti, P. Nonsteroidal aromatase inhibitors: recent advances. Med. Res. Rev. 2002, 22, 282-304.
48. Li, M.; Ciu, J.-R.; Ye, Y.; Min, J.-M.; Zhang, L.-H.; Wang, K.; Gares, M.; Cros, J.; Wright, M.; Leung-Tack, J. Antitumor activity of Z-ajoene, a natural compound purified from garlic: antimitotic and microtubule-interaction properties. Carcinogenesis 2002, 23 (4), 573-9.
49. Lehmann, L.; Metzler, M. Bisphenol A and its methylated congeners inhibit growth and interfere with microtubules in human fibroblast in vitro. Chem.-Biol. Interact. 2004, 147, 273-285.
50. Jonnalagadda, S. S.; ter Haar, E.; Hamel, E.; Lin, C. M.; Magarian, R. A.; Day, B. W. Synthesis and biological evaluation of 1,1-dichloro-2,3- diarylcyclopropanes as antitubulin and antibreast cancer agents. Bioorg., Med. Chem. 1997, 5, 715-22.
51. Bradford, M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 1976, 72, 248-254.
52. Barzon, L.; Bonaguro, R.; Castagliuolo, I.; Chiosi, M.; Gnatta, E.; Parolin, C.; Boscaro, M.; Palù, G. Transcriptionally targeted retroviral vector for combined suicide and immunomodulating gene therapy of thyroid cancer. J. Clin. Endocrinol. Metab. 2002, 87, 5304-11.