Design and Synthesis of Rac1 inhibitors as Potential Antitumor Agents

CIARLANTINI, M; NAZARENO GONZÁLEZ; LUCAS DEFELIPE; GANDOLFI-DONADÍO L; ADRIAN G. TURJANSKI; PABLO LORENZANO MENNA; MARIA J. COMIN

Campos do Jordão, Brasil

Congreso; The 7th Brazilian Symposium on Medicinal Chemistry (BrazMedChem2014); 2014

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.1 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 and the synthesis and evaluation of new analogues.