4-oxoquinoline-3-carboxamide acyclonucleoside phosphonates hybrids: Human MCF-7 breast cancer cell death induction by oxidative stress-promoting and in silico ADMET studies

• Published in: Journal of molecular structure Vol. 1276; p. 134542
• Main Authors: Machado, Thayná R., Faro, Letícia V., Mello, Angélica L.do Nascimento, Silva, David de O., Abrahim-Vieira, Bárbara de A., Rodrigues, Carlos R., Silva, Rita Hemanuelle S., Junior, Claudio S.Viana, Sola-Penna, Mauro, Boechat, Fernanda da C.S., de Souza, Marcos C., Zancan, Patricia, de Souza, Maria Cecília B.V., de Souza, Alessandra M.T.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15-03-2023
• Subjects: 4-oxoquinoline; Acyclonucleoside phosphonate; Antitumor agents; Breast cancer; In silico toxicology; Acyclonucleoside phosphonate; Breast cancer; In silico toxicology; Antitumor agents; 4-oxoquinoline
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2022.134542

•Compounds 15a-k were synthesized as antitumoral agents.•15c, 15e, 15g, and 15k showed significant cytotoxicity.•15c, g, and k increased the levels of reactive species and superoxide ions.•In silico toxicity screening showed that 15g presented low hepatotoxicity risk.•15g is a potential candidate to optimize for the development of anticancer agents.
Breast cancer is the leading cause of cancer death in women. Although the available treatments are efficient, cancer cells promptly develop resistance to different drugs, leading to disease relapse and promoting tumor progression. Here, novel 4-oxoquinoline-3-carboxamide acyclonucleoside phosphonate hybrids were synthesized as antitumoral agents, and in silico toxicity screening were performed. Derivatives 15c, 15e, 15g, and 15k showed significant cytotoxicity where 15c induces the most considerable loss of cell viability through the apoptotic process, while 15k induces cell death by necrosis. All compounds, except 15e, induced the production of OH- and NO, besides increasing the levels of superoxide ions. In silico toxicity studies showed that 15g presented low hepatotoxicity risk and probability as BCRP substrate. These findings point out that derivative 15g is a potential candidate for an optimization program for the development of new anticancer agents.
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