Novel Oxadiazole-Quinoxalines as Hybrid Scaffolds with Antitumor Activity

Corona, Paola;Gessi, Stefania;Ibba, Roberta;Merighi, Stefania;Mirandola, Prisco;Pinna, Gérard Aimè;Nigro, Manuela;Pozzi, Giulia;Asproni, Battistina;Travagli, Alessia;Piras, Sandra;Carta, Antonio;Caria, Paola;Murineddu, Gabriele

2025-01-01

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Abstract

A small library of 25 novel 1,3,4-oxadiazole-quinoxalines was synthesized and evaluated in vitro for its cytotoxic activity at 10 μM concentration against nine NCI-different cancer cell lines. Among tested compounds, derivatives 24, 25, and 26 showed good inhibition percentages over different cell lines and, therefore, progressed to the full five-dose assay. Compound 24, possessing a 1,3,4-oxadiazole-core, bearing a 7-trifluoromethyl-quinoxaline nucleus on C-2 and a C-5 phenyl ring, had activity against leukemia, CNS, ovarian, renal, prostate, and breast cancer, with highest the values against breast MCF7 (GI50: 1.85 μM) and MDA-MB-468 (GI50: 1.95 μM) cell lines, showing the better MG_MID value (−5.02). These novel derivatives were able to delay the S phase of the cell cycle and induce apoptosis.