Synthesis and development of novel small molecules targeting Rac1 signaling as new potential leads for antitumor agents

Synthesis and development of novel small molecules targeting Rac1 signaling as new potential leads for antitumor agents

Ciarlantini, M.; Gonzalez, N; Cardama, G. A.; Defelipe, L.; Turjanski, A.; Alonso, D. F.; Gomez, D. E.; Lorenzano Menna, P.; Comin, M. J.

Abstract:

Rho GTPases are a family of small GTP-binding proteins involved in cell cytoskeleton organization, migration, transcription, and proliferation. They act as molecular switches that cycle between an inactive GDP-bound and an active GTP-bound form. Guanine nucleotide exchange factors (GEFs) highly regulates this process. The active GTP-bound state binds preferentially to downstream effectors proteins and actively transduces signals. The aberrant activation of Rac1, one of the most studied Rho GTPases, is involved in tumor progression, invasion and metastasis and it is considered a promising target for novel anticancer drug development. We present the identification of a hit structure, ZINC69391 (1) and the synthesis and evaluation of new analogues.

Rho GTPases are a family of small GTP-binding proteins involved in cell cytoskeleton organization, migration, transcription, and proliferation. They act as molecular switches that cycle between an inactive GDP-bound and an active GTP-bound form. Guanine nucleotide exchange factors (GEFs) highly regulates this process. The active GTP-bound state binds preferentially to downstream effectors proteins and actively transduces signals. The aberrant activation of Rac1, one of the most studied Rho GTPases, is involved in tumor progression, invasion and metastasis and it is considered a promising target for novel anticancer drug development. We present the identification of a hit structure, ZINC69391 (1) and the synthesis and evaluation of new analogues.

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DOI: 10.5151/chempro-15bmos-BMOS2013_2013823102916

Referências bibliográficas

• [1] 1 Etienne-Manneville, S.; Hall, A. Nature, 2002 420(6916),629.
• [2] 2 Fritz, G.; Kaina, B. Curr Cancer Drug Targets, 2006. 6(1),1.

Como citar:

Ciarlantini, M.; Gonzalez, N; Cardama, G. A.; Defelipe, L.; Turjanski, A.; Alonso, D. F.; Gomez, D. E.; Lorenzano Menna, P.; Comin, M. J.; "Synthesis and development of novel small molecules targeting Rac1 signaling as new potential leads for antitumor agents", p-200-200. 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_2013823102916