Design, synthesis and cytotoxic evaluation of a library of oxadiazole and isoxazole-containing hybrids.

CAMACHO C; PIZZIO MG; ROCES DL; BOGGIÁN D.B; MATA E.G.; BELLIZZI YANINA; BARRIONUEVO E; BLANK VC; ROGUIN LP

RSC Advances

Royal Society of Chemistry

Lugar: Cambridge; Año: 2021 vol. 11 p. 29741 - 29751

2046-2069

The development of hybrid compounds led to the discovery of new pharmacologically active agents forsome of the most critical diseases, including cancer. Herein, we describe a new series of oxadiazolecontainingstructures designed by a molecular hybridization approach. Penicillin derivatives and aminoacids were linked to amino acid and aromatic moieties through the formation of a 1,2,4-oxadiazole ring.Alternatively, condensation between amino acid-derived hydrazides and an activated penicillanic acid ledto a series of 1,3,4-oxadiazole penicillin-containing hybrids and non-cyclized diacylhydrazides. From thecytotoxicity assays it is highlighted that two 1,2,4-oxadiazoles and one 1,3,4-oxadiazole connectinga penicillin and aliphatic amino acids displayed a high degree of cytotoxic selectivity, ranging betweenbeing three and four times more potent against tumor cells than normal cells. The results give a veryinteresting perspective suggesting that these hybrid compounds can offer a novel antitumor scaffoldwith promising cytotoxicity profiles.