Pyrimido[1,2- a]quinoxaline 6-oxide and phenazine 5,10-dioxide derivatives and related compounds as growth inhibitors of Trypanosoma cruzi

• Published in: European journal of medicinal chemistry 2008-08, Vol.43 (8), p.1737-1741
• Main Authors: Lavaggi, María Laura, Aguirre, Gabriela, Boiani, Lucía, Orelli, Liliana, García, Beatriz, Cerecetto, Hugo, González, Mercedes
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimalarials - chemical synthesis; Antimalarials - chemistry; Antimalarials - pharmacology; Antiparasitic agents; Biological and medical sciences; Chagas disease; Cyclic N-Oxides - chemical synthesis; Cyclic N-Oxides - chemistry; Cyclic N-Oxides - pharmacology; Electrons; Inhibitory Concentration 50; Medical sciences; Molecular Structure; Pharmacology. Drug treatments; Phenazine 5,10-dioxide; Phenazines - chemical synthesis; Phenazines - chemistry; Phenazines - pharmacology; Pyrimido[1,2-a]quinoxaline 6-oxide; Quinoxalines - chemical synthesis; Quinoxalines - chemistry; Quinoxalines - pharmacology; Structure-Activity Relationship; Trypanosoma cruzi - cytology; Trypanosoma cruzi - drug effects
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2007.10.031

Two different families of N-oxide containing heterocycles were evaluated as in vitro growth inhibitors of T. cruzi. Both families of heterocycles were selected from our in-house library of compounds as analogues of active anti- T. cruzi N-oxide containing heterocycles. Derivatives from pyrimido[1,2- a]quinoxaline 6-oxide family were poorly active at the assayed doses. However, phenazine 5,10-dioxide derivatives displayed good to excellent anti- T. cruzi activities. The anti- T. cruzi activity of phenazine derivatives was related to substituent' electronic descriptors, σ p −. Derivatives 19, 20 and 23 were the most cytotoxic compounds against the protozoan and became excellent hit for further structural modifications. Two series of N-oxide containing heterocycles were studied as anti- T. cruzi agents. Phenazine 5,10-dioxide derivatives with relevant in vitro activity were identified. [Display omitted]