Strategies for the Generation of Triazolylpeptidyl Penicillin Analogs in the Search for New Antitumoral Compounds ?

NADIA L. MARTIREN ; YANINA BELLIZZI; ELIZABETH BARRIONUEVO; VIVIANA C BLANK; LEONOR P. ROGUIN; ERNESTO G. MATA; PATRICIA G. CORNIER

Congreso; 6ta Reunión Internacional de Ciencias Farmacéuticas (RICiFa 2020+1); 2021

Molecular hybridization methodology and solid-phase organic synthesis were employed by our research group to afford a library of compounds that conjugate a penicillin moiety with amino acids through a triazole group. These triazolylpeptidyl penicillins were evaluated as antiproliferative agents? in vitro showing an outstanding activity and selectivity. Motivated by these previous results, we design three sets of peptoid analogs with strategic modifications aiming at different goals. One approach is based on N-substituted glycine, to study the performance of these bioisosteres. Another strategy was the substitution of triazole moiety with a glycine monomer to assess the effect of this particular heterocycle on the biological activity. And finally, we have developed a new approach to generate the triazole group, in order to simplify the synthetic path. The desired compounds were synthesize employing mainly a solid-phase approach and the cytotoxic effect evaluated against the B16-F0 cell line and compared with the effects on normal murine mammary gland cells (NMuMG). A library of peptoid derivatives was obtained in good yields and a preliminary structure activity relationship was investigated.