Antitumor agents 288: Design, synthesis, SAR, and biological studies of novel heteroatom-incorporated antofine and cryptopleurine analogues as potent and selective antitumor agents

Journal of Medicinal Chemistry

Volumn 54, Issue 14, 2011, Pages 5097-5107

  Yang, Xiaoming ^a   Shi, Qian ^a   Yang, Shuenn Chen ^b   Chen, Chi Yuan ^b   Yu, Sung Liang ^c,e   Bastow, Kenneth F ^a   Morris Natschke, Susan L ^a   Wu, Pei Chi ^a   Lai, Chin Yu ^c   Wu, Tian Shung ^f   Pan, Shiow Lin ^c   Teng, Che Ming ^c   Lin, Jau Chen ^b   Yang, Pan Chyr ^b,c,d   Lee, Kuo Hsiung ^a,f  

^a UNC Hamner Institute for Drug Safety Sciences   (United States)

^b INSTITUTE OF BIOMEDICAL SCIENCES   (Taiwan)

^c NATIONAL TAIWAN UNIVERSITY   (Taiwan)

^d NATIONAL TAIWAN UNIVERSITY   (Taiwan)

^e NATIONAL TAIWAN UNIVERSITY HOSPITAL   (Taiwan)

^f CHINA MEDICAL UNIVERSITY   (Taiwan)

Author keywords

[No Author keywords available]

Indexed keywords

12 OXA CRYPTOPLEURINE; 13 OXA CRYPTOPLEURINE; 13N BOC 11 OXO 13 AZA CRYPTOPLEURINE; 13N BOC 13 AZA CRYPTOPLEURINE; 2 (6,7,10 TRIMETHOXY 1,2,3,4 TETRAHYDRODIBENZO[F,H]ISOQUINOLIN 3 YL)ACETALDEHYDE; 6,7,10 TRIMETHOXY 3 (2 METHOXYVINYL) 1,2,3,4 TETRAHYDRODIBENZO[F,H]ISOQUINOLINE; ANTINEOPLASTIC AGENT; ANTOFINE; CRYPTOPLEURINE; NATURAL PRODUCT; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL CULTURE; CANCER INHIBITION; CELL CYCLE S PHASE; CELL STRAIN HT29; COLORECTAL CARCINOMA; CONTROLLED STUDY; CYTOTOXICITY; DNA REPLICATION; DRUG DESIGN; DRUG MECHANISM; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; IN VITRO STUDY; MALE; MOUSE; NASOPHARYNX CANCER; NONHUMAN; PROSTATE CANCER; REGULATORY MECHANISM; STRUCTURE ACTIVITY RELATION; TUMOR XENOGRAFT; UMBILICAL VEIN ENDOTHELIAL CELL;

ALKALOIDS; ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; DNA REPLICATION; DRUG DESIGN; DRUG SCREENING ASSAYS, ANTITUMOR; INDOLES; MICE; NEOPLASM TRANSPLANTATION; PHENANTHROLINES; S PHASE; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; TRANSPLANTATION, HETEROLOGOUS;

EID: 79960625636     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm200330s     Document Type: Article

References (34)

1. Gellert, E. The indolizidine alkaloids J. Nat. Prod. 1982, 45 (1) 50-73 (Pubitemid 12102893)
2. Xi, Z.; Zhang, R.; Yu, Z.; Ouyang, D. The interaction between tylophorine B and TMV RNA Bioorg. Med. Chem. Lett. 2006, 16 (16) 4300-4304
3. Wang, K.; Su, B.; Wang, Z.; Wu, M.; Li, Z.; Hu, Y.; Fan, Z.; Mi, N.; Wang, Q., Synthesis and antiviral activities of phenanthroindolizidine alkaloids and their derivatives. J. Agric. Food Chem. 2010, 58 (5), 2703-2709.
4. Baumgartner, B.; Erdelmeier, C. A. J.; Wright, A. D.; Rali, T.; Sticher, O. An antimicrobial alkaloid from Ficus septica Phytochemistry 1990, 29 (10) 3327-3330
5. Bhutani, K. K.; Sharma, G. L.; Ali, M. Plant based antiamoebic drugs; Part I. Antiamoebic activity of phenanthroindolizidine alkaloids; common structural determinants of activity with emetine Planta Med. 1987, 53 (6) 532-536 (Pubitemid 18004293)
6. Banwell, M. G.; Bezos, A.; Burns, C.; Kruszelnicki, I.; Parish, C. R.; Su, S.; Sydnes, M. O. C8c-C15 monoseco-analogues of the phenanthroquinolizidine alkaloids julandine and cryptopleurine exhibiting potent anti-angiogenic properties Bioorg. Med. Chem. Lett. 2006, 16 (1) 181-185 (Pubitemid 41630626)
7. Yang, C.-W.; Chen, W.-L.; Wu, P.-L.; Tseng, H.-Y.; Lee, S.-J. Anti-inflammatory mechanisms of phenanthroindolizidine alkaloids Mol. Pharmacol. 2006, 69 (3) 749-758 (Pubitemid 43363849)
8. Yang, C.-W.; Chuang, T.-H.; Wu, P.-L.; Huang, W.-H.; Lee, S.-J. Anti-inflammatory effects of 7-methoxycryptopleurine and structure-activity relations of phenanthroindolizidines and phenanthroquinolizidines Biochem. Biophys. Res. Commun. 2007, 354 (4) 942-948 (Pubitemid 46216224)
9. NCI 60-cell assay results can be found at http://dtp.nci.nih.gov/ dtpstandard/dwindex/index.jsp.
10. Gao, W.; Lam, W.; Zhong, S.; Kaczmarek, C.; Baker David, C.; Cheng, Y.-C. Novel mode of action of tylophorine analogs as antitumor compounds Cancer Res. 2004, 64 (2) 678-688 (Pubitemid 38120910)
11. Li, Z.; Jin, Z.; Huang, R. Isolation, total synthesis and biological activity of phenanthroindolizidine and phenanthroquinolizidine alkaloids Synthesis 2001, 16, 2365-2378 (Pubitemid 33131974)
12. Chemler, S. R. Phenanthroindolizidines and phenanthroquinolizidines: promising alkaloids for anti-cancer therapy Curr. Bioact. Compd. 2009, 5 (1) 2-19
13. Cusack, J. C., Jr. ; Liu, R.; Baldwin, A. S., Jr. Inducible chemoresistance to 7-ethyl-10-[4-(1-piperidino)-1-piperidino]- carbonyloxycamptothe cin (CPT-11) in colorectal cancer cells and a xenograft model is overcome by inhibition of nuclear factor-kappaB activation Cancer Res. 2000, 60 (9) 2323-2330 (Pubitemid 30262414)
14. Huang, M. T.; Grollman, A. P. Mode of action of tylocrebrine-effects on protein and nucleic-acid synthesis Mol. Pharmacol. 1972, 8 (5) 538-550
15. Gupta, R. S.; Siminovitch, L. Mutants of CHO cells resistant to the protein synthesis inhibitors, cryptopleurine and tylocrebrine: genetic and biochemical evidence for common site of action of emetine, cryptopleurine, tylocrebrine, and tubulosine Biochemistry 1977, 16 (14) 3209-3214 (Pubitemid 8134434)
16. Gupta, R. S.; Krepinsky, J. J.; Siminovitch, L. Structural determinants responsible for the biological activity of (-)-emetine, (-)-cryptopleurine, and (-)-tylocrebrine: structure-activity relationship among related compounds Mol. Pharmacol. 1980, 18 (1) 136-143 (Pubitemid 10093098)
17. Dolz, H.; Vazquez, D.; Jimenez, A. Quantitation of the specific interaction of [14a-3H]cryptopleurine with 80S and 40S ribosomal species from the yeast Saccharomyces cerevisiae Biochemistry 1982, 21 (13) 3181-3187 (Pubitemid 12065488)
18. Cai, X. F.; Jin, X.; Lee, D.; Yang, Y. T.; Lee, K.; Hong, Y.-S.; Lee, J.-H.; Lee, J. J. Phenanthroquinolizidine alkaloids from the roots of Boehmeria pannosa potently inhibit hypoxia-inducible factor-1 in AGS human gastric cancer cells J. Nat. Prod. 2006, 69 (7) 1095-1097 (Pubitemid 44252229)
19. Rao, K. N.; Bhattacharya, R. K.; Venkatachalam, S. R. Inhibition of thymidylate synthase and cell growth by the phenanthroindolizidine alkaloids pergularinine and tylophorinidine Chem.-Biol. Interact. 1997, 106 (3) 201-212 (Pubitemid 27515087)
20. Rao, K. N.; Bhattacharya, R. K.; Veankatachalam, S. R. Inhibition of thymidylate synthase by pergularinine, tylophorinidine and deoxytubulosine Indian J. Biochem. Biophys. 1999, 36 (6) 442-448 (Pubitemid 129490552)
21. Rao, K. N.; Venkatachalam, S. R. Inhibition of dihydrofolate reductase and cell growth activity by the phenanthroindolizidine alkaloids pergularinine and tylophorinidine: the in vitro cytotoxicity of these plant alkaloids and their potential as antimicrobial and anticancer agents Toxicol. in Vitro 2000, 14 (1) 53-59 (Pubitemid 30122814)
22. Gao, W.; Chen, A. P.-C.; Leung, C.-H.; Gullen, E. A.; Fuerstner, A.; Shi, Q.; Wei, L.; Lee, K.-H.; Cheng, Y.-C. Structural analogs of tylophora alkaloids may not be functional analogs Bioorg. Med. Chem. Lett. 2008, 18 (2) 704-709
23. Suffness, M.; Douros, J. Anticancer Agents Based on Natural Product Models; Academic Press: New York, 1980; pp 465-487.
24. Gao, W.; Bussom, S.; Grill, S. P.; Gullen, E. A.; Hu, Y.-C.; Huang, X.; Zhong, S.; Kaczmarek, C.; Gutierrez, J.; Francis, S.; Baker, D. C.; Yu, S.; Cheng, Y.-C. Structure-activity studies of phenanthroindolizidine alkaloids as potential antitumor agents Bioorg. Med. Chem. Lett. 2007, 17 (15) 4338-4342 (Pubitemid 47021384)
25. Wei, L.; Shi, Q.; Bastow Kenneth, F.; Brossi, A.; Morris-Natschke Susan, L.; Nakagawa-Goto, K.; Wu, T.-S.; Pan, S.-L.; Teng, C.-M.; Lee, K.-H. Antitumor agents 253. Design, synthesis, and antitumor evaluation of novel 9-substituted phenanthrene-based tylophorine derivatives as potential anticancer agents J. Med. Chem. 2007, 50 (15) 3674-3680 (Pubitemid 47195473)
26. Lin, J. C.; Yang, S. C.; Hong, T. M.; Yu, S. L.; Shi, Q.; Wei, L.; Chen, H. Y.; Yang, P. C.; Lee, K. H. Phenanthrene-based tylophorine-1 (PBT-1) inhibits lung cancer cell growth through the Akt and NF-kappaB pathways J. Med. Chem. 2009, 52 (7) 1903-1911
27. Yang, X.; Shi, Q.; Liu, Y. N.; Zhao, G.; Bastow, K. F.; Lin, J. C.; Yang, S. C.; Yang, P. C.; Lee, K. H. Antitumor agents 268. Design, synthesis, and mechanistic studies of new 9-substituted phenanthrene-based tylophorine analogues as potent cytotoxic agents J. Med. Chem. 2009, 52 (16) 5262-5268
28. Wang, K.; Wang, W.; Wang, Q.; Huang, R. Efficient synthesis of aza-phenanthroindolizidine and aza-phenanthroquinolizidine and anticancer activities Lett. Org. Chem. 2008, 5 (5) 383-390
29. Yang, X. M.; Shi, Q.; Bastow, K. F.; Lee, K. H. Antitumor Agents. 274. A new synthetic strategy for E-ring SAR study of antofine and cryptopleurine analogues Org. Lett. 2010, 12 (7) 1416-1419
30. Alavijeh, M. S.; Chishty, M.; Qaiser, M. Z.; Palmer, A. M. Drug metabolism and pharmacokinetics, the blood-brain barrier, and central nervous system drug discovery NeuroRx 2005, 2 (4) 554-571 (Pubitemid 41393265)
31. Clark, D. E. In silico prediction of blood-brain barrier permeation Drug Discovery Today 2003, 8 (20) 927-933 (Pubitemid 37230012)
32. van de Waterbeemd, H.; Camenisch, G.; Folkers, G.; Chretien, J. R.; Raevsky, O. A. Estimation of blood-brain barrier crossing of drugs using molecular size and shape, and H-bonding descriptors J. Drug Target 1998, 6 (2) 151-165 (Pubitemid 29033982)
33. http://preadmet.bmdrc.org
34. Wang, Y.; Gao, W.; Svitkin, Y. V.; Chen, A. P.; Cheng, Y. C. DCB-3503, a tylophorine analog, inhibits protein synthesis through a novel mechanism PLoS One 2010, 5 (7) e11607