Synthesis of Diaryl Pyrrolones Derivatives as Combretastatin A-4

Abstract:

Combretastatins-A4 (CA-4) is a natural product with anticancer activity. However, only the cis-isomer exhibits strong antitubulin activity, but the cis-isomer tends to isomerize to the inactive trans-isomer. Thus, this paper reports that an additional pyrrolidone ring was used to replace the cis double bond to arrest the cis-conformation, and a series of 3,4-diaryl pyrrolediones and 3,4-diaryl pyrrolones as CA-4 analogues were synthesized via a four steps reaction from 3,4-dimethoxyacetophenone and 3-fluoro-4-methoxy acetophenone. The structure of the new compounds was confirmed by 1H NMR, 13C NMR, ESI-MS and elemental analysis. The in vitro activities of CA-4 analogues against HL-60, SMMC-7721 and A549 human cancer cell lines were tested using colorimetric MTT assay and the results indicate that they show significant antitumor activity.

• Periodical: Advanced Materials Research (Volumes 652-654)
• Pages: 689-692
• DOI: https://doi.org/10.4028/www.scientific.net/AMR.652-654.689
• Online since: January 2013
• Authors: Li Wei, Guo Yuan Lu
• Keywords: Antitumor Activity, Combretastatin Analogues, Diaryl Pyrrolone, Synthesis

References

[1] G.R. Pettit, S.B. Singh, M.L. Niven, E. Hamel, J.M. Schmidt: J. Nat. Prod. Vol. 50(1987), p.119–131.

[2] G. M. Tozer, C. Kanthou, B. C. Baguley: Nat. Rev. Cancer, Vol. 5(2005), p.423–425.

[3] G. R. Pettit, C., Jr. Temple, V. L. Narayanan: Anticancer Drug Res. Vol. 10(1995), p.299–309.

[4] P. E. Thorpe, D. J. Chaplin, D.C. Blakey: Cancer Research, (2003), pp.1144-1147.

[5] G. R. Pettit, M. R. Rhodes, D. L. Herald, D. J. Chaplin, M. R. L. Stratford, E. Hamel, R. K. Pettit, J. -C. Chapuis, D. Oliva: Anti-Cancer Drug Res. Vol. 13(1998), p.981–993.

[6] L. Wang, K. W. Woods, Q. Li, K. J. Barr, R. W. McCroskey, S. M. Hannick, L. Gherke, R. B. Credo, Y. -H. Hui, K. Marsh, R. Warner, J. Y. Lee, N. Zielinsky-Mozng, D. Frost, S. H. Rosenberg, H. L. Sham: J. Med. Chem. Vol45(2002), p.1697–1711.

DOI: 10.1021/jm010523x

[7] C.M. Sun, L.G. Lin, H.J. Yu, C.Y. Cheng, Y.C. Tsai, C.W. Chu, Y.H. Din, Y.P. Chau, M.J. Don: Bioorg. Med. Chem. Lett. Vol. 17(2007), pp.1078-1081.

[8] K. Ohsumi, T. Hatanaka, K. Fujita, R. Nakagawa, Y. Fukuda, Y. Nihei, Y. Suga, Y. Morinaga, Y. Akiyama, T. Tsuji: Bioorg. Med. Chem. Lett. Vol. 8(1998), p.3153–3158.

DOI: 10.1016/s0960-894x(98)00579-4

[9] R. LeBlanc, J. Dickson, T. Brown, M. Steward, H. N. Pati, D. VanDerveer, H. Arman, J. Harris, W. Pennington, H. L. Jr. Holt, M. Lee: Bioorg. Med. Chem. Vol. 13(2005), p.6025–6034.

DOI: 10.1016/j.bmc.2005.06.028

[10] R. Romeo, G. B. Pier, C. L. Olga: J. Med. Chem. Vol. 53(2010), pp.4248-4258.

[11] L. Lee, L.M. Robb, M. Lee, R. Davis, H. Mackay, S. Chavda, B. Babu, E. L. O'Brien, A. L. Risinger, S. L. Mooberry, M. Lee: J. Med. Chem. Vol. 53(2010), p.325–334.

DOI: 10.1021/jm901268n

[12] C. Peifer, T. Stoiber, E. Unger, F. Totzke, C. Schachtele, D. Marme, R. Brenk, G. Klebe, D. Schollmeyer, G. Dannhardt: J. Med. Chem. Vol. 49(2006), pp.1271-1281.

DOI: 10.1021/jm0580297

[13] M. Pal, N. K. Swamy, P. S. Hameed, S. Padakanti, K. R. Yeleswarapu: Tetrahedron, Vol. 60(2004), p.3987–3997.

DOI: 10.1016/j.tet.2004.03.036

[14] W. Song, X-F. Lu, G-Y. Lu: Chem. J. Chin. Univ. (In Chinese) Vol. 27(2006), pp.460-463.

[15] J. M. Sargent, C. G. Taylor, Ber. J. Cancer, Vol. 60(1989), p.206–210.