Synthesis of new N,S-acetal analogs derived from juglone with cytotoxic activity against Trypanossoma cruzi

• Published in: Journal of bioenergetics and biomembranes Vol. 52; no. 3; pp. 199 - 213
• Main Authors: Pacheco, Paulo Anastácio Furtado, de Menezes Ribeiro, Thais, dos Santos Galvão, Raíssa Maria, dos Santos, Eldio Gonçalves, Faria, Ana Flávia Martins, von Ranke, Natalia Lidmar, Bello, Murilo Lamim, Rodrigues, Carlos Rangel, Ferreira, Vitor Francisco, Souza, André Luis Almeida, de Jesús Hardoim, Daiana, da Silva Calabrese, Katia, Faria, Robson Xavier, da Rocha, David Rodrigues
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2020; Springer Nature B.V
• Subjects: Analogs; Animal Anatomy; Animal Biochemistry; Benznidazole; Biochemistry; Bioorganic Chemistry; Chemistry; Chemistry and Materials Science; Cytotoxicity; Histology; Irradiation; Juglone; Morphology; Organic Chemistry; Prototypes; Selectivity; acetal; Naphtoquinones; N,S-acetal; Trypanosoma cruzi
• ISSN: 0145-479X; 1573-6881
• DOI: 10.1007/s10863-020-09834-8

A series of 11 new N,S -acetal juglone derivatives were synthesized and evaluated against T. cruzi epimastigote forms. These compounds were obtained in good to moderate yields using a microwave irradiation protocol. Among all compounds, two N,S -acetal analogs, showed significant trypanocidal activity. Notably, one compound 11g exhibited selectivity index 10-fold higher than the reference drug benznidazole for epimastigote. The compound 11h was more effective for amastigote forms. Both prototypes exhibited S.I. higher than the benznidazole description. Thus, both compounds proving to be useful candidate molecules to further studies in infected animals.