Discovery and synthesis of a new analogues of the cyclopenta[b]indoles as tubulin polymerization inhibitors

Discovery and synthesis of a new analogues of the cyclopenta[b]indoles as tubulin polymerization inhibitors

Fernandes, D. C.; Santos, R. N. S.; Júnior, M. T. R; Andricopulo, A. D.; Coelho, F.

Abstract:

Cancer is a disease characterized by rapid and abnormal cell division and migration of tumor cells to other body organs. The development of small molecule modulators that interfere with microtubule dynamics through of the interaction with the tubulin is a particularly valid approach in cancer chemotherapy. Recently, the search for simpler polymerization inhibitors agents has renewed the interest in the development of colchicine analogs, sometimes discarded for their high toxicity. In this context, a series of substances synthesized from Morita-Baylis-Hillman adducts (258 compounds) was screened using molecular docking. Application of physico-chemical filters guided the selection of a focused collection of cyclopenta[b]indole derivatives as potential microtubule polymerization inhibitors. Therefore, to improve the interaction between the cyclopenta[b]indole skeleton and the residues of colchicine sites, new analogs of this compounds have been designed and synthesized.

Cancer is a disease characterized by rapid and abnormal cell division and migration of tumor cells to other body organs. The development of small molecule modulators that interfere with microtubule dynamics through of the interaction with the tubulin is a particularly valid approach in cancer chemotherapy. Recently, the search for simpler polymerization inhibitors agents has renewed the interest in the development of colchicine analogs, sometimes discarded for their high toxicity. In this context, a series of substances synthesized from Morita-Baylis-Hillman adducts (258 compounds) was screened using molecular docking. Application of physico-chemical filters guided the selection of a focused collection of cyclopenta[b]indole derivatives as potential microtubule polymerization inhibitors. Therefore, to improve the interaction between the cyclopenta[b]indole skeleton and the residues of colchicine sites, new analogs of this compounds have been designed and synthesized.

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DOI: 10.5151/chempro-15bmos-BMOS2013_2013103173553

Referências bibliográficas

• [1] 1Zhao, H. et al. Cancer Letters, 2012, 314, 54.
• [2] 2Baylis, A. B.; Hillman, M. E. D. German Patent 2155113, 1972 (C.A.. 1972, 77, 34174q).
• [3] 3Coelho, F. et al. Tetrahedron, 2002, 58, 7437.

Como citar:

Fernandes, D. C.; Santos, R. N. S.; Júnior, M. T. R; Andricopulo, A. D.; Coelho, F.; "Discovery and synthesis of a new analogues of the cyclopenta[b]indoles as tubulin polymerization inhibitors", p-137-137. In: In Blucher Chemistry Proceedings, São Paulo, v. 1, n. 2, Dezembro.2013. São Paulo: Blucher, 2013.
ISSN 23184043, DOI 10.5151/chempro-15bmos-BMOS2013_2013103173553