Synthesis of naphtho[2,3-a]phenoxazinium chlorides: Structure–activity relationships of these heterocycles and benzo[a]phenoxazinium chlorides as new antimicrobials

Abstract

Synthesised functionalised naphtho[2,3-a]phenoxazinium chlorides revealed great fluorescence with maximum emission wavelengths between 630 and 676 nm, in ethanol and water at physiological pH. Naphtho[2,3-a]phenoxazines, as well as a series of benzo[a]phenoxazines, were evaluated against Saccharomyces cerevisiae, in a broth microdilution assay. This family of compounds exhibited antifungal activity depending both on the substituents of the heterocycle nucleus as well as on its size. The best activities were obtained for four-ring systems, and particularly for 5,9-diaminobenzo[a]phenoxazines with R=Me, R(1)=H and R(2)=Et. As for R(3) substitution, the greatest efficiency was obtained for R(3)=(CH(2))(3)Cl, with a MIC of 3.75 microM. The linkage of different amino acids to the functional group of the 5-amino position of diaminobenzo[a]phenoxazinium moiety resulted in compounds with diverse antimicrobial efficiencies, depending on the polar character of the amino acid, on its linkage position and on the size of the alkyl chain linker.