Synthesis of Combretastatin A-4 Analogs with Antitumoral Properties

Synthesis of Combretastatin A-4 Analogs with Antitumoral Properties

Bezerra, Natércia M. M.; Militão, Gardênia C. G.; Silva, Terezinha G. da; Menezes, Paulo H.; Oliveira, Roberta A.

Abstract:

Combretastatin A-4 (CA-4) (Figure 1), a natural Zstilbene isolated from the South African willow Combretum caffrum, has been found to strongly inhibit the tubulin assembly by binding to the colchicine site and to be a cytotoxic agent against a wide variety of cell lines, including multidrugresistant lines. The structural simplicity of CA-4 combined with its excellent antitumor and antivascular activities encouraged the scientific community to synthesize numerous analogs. From these structure–activity relationship (SAR) investigations, it has been established that the cis-orientation of the two aryl rings is crucial for the activity of CA-4 as well as the trimethoxyaryl unit, whereas, the hydroxyl group on the 3’-position is not essential. Consequently, the synthesis of CA-4 analogs for further studies of their biological activities is of the great interest.

Combretastatin A-4 (CA-4) (Figure 1), a natural Zstilbene isolated from the South African willow Combretum caffrum, has been found to strongly inhibit the tubulin assembly by binding to the colchicine site and to be a cytotoxic agent against a wide variety of cell lines, including multidrugresistant lines. The structural simplicity of CA-4 combined with its excellent antitumor and antivascular activities encouraged the scientific community to synthesize numerous analogs. From these structure–activity relationship (SAR) investigations, it has been established that the cis-orientation of the two aryl rings is crucial for the activity of CA-4 as well as the trimethoxyaryl unit, whereas, the hydroxyl group on the 3’-position is not essential. Consequently, the synthesis of CA-4 analogs for further studies of their biological activities is of the great interest.

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DOI: 10.5151/chempro-14bmos-R0272-1

Referências bibliográficas

• [1] 1 Pettit, G. R.; Singh, S. G.; Boyd, M. R.; Hamel, E.; Pettit, R. K.; Schmidt, J. M.; Hogan, F. J. Med. Chem. 1995, 38,1666.
• [2] 2 Cella, R.; Stefani, H. A. Tetrahedron 2006, 62, 5656.

Como citar:

Bezerra, Natércia M. M.; Militão, Gardênia C. G.; Silva, Terezinha G. da; Menezes, Paulo H.; Oliveira, Roberta A.; "Synthesis of Combretastatin A-4 Analogs with Antitumoral Properties", p-272-272. In: In Blucher Chemistry Proceedings, São Paulo, v. 1, n. 1, Setembro.2013. São Paulo: Blucher, 2013.
ISSN 23184043, DOI 10.5151/chempro-14bmos-R0272-1