Imidazolidines as new anti-Trypanosoma cruzi agents: biological evaluation and structure-activity relationships.

Imidazolidine derivatives were studied as anti-Trypanosoma cruzi agents. Imidazolines can be considered as ethylenediamine/carbonyl precursors and therefore interfere with the biosynthesis of polyamines into the parasite. Some of the derivatives were found to have high and selective activity against the proliferative stages of the parasite, with IC(50) values against the epimastigote form in the low micromolar range as the reference drug Nifurtimox. The imidazolidines demonstrated to be stable after five days of incubation in buffer glucose, pH 7, indicating that diamines were not obtained in these conditions. But it was found that two of the studied diamine precursors were as active as the parent compounds. Probably, the imidazolidines affect the mitochondrial integrity according to the excreted end-products found in the NMR studies. The QSAR studies indicated that the bioactivities are correlated with the lipophilicities. In conclusion, we have described a new and relevant bioactivity for imidazolidines. The results support further in vivo studies of some of these imidazolidine derivatives.

A comparison of the electron ionization and electrospray behaviour of some N,N'-disubstituted hexahydropyrimidines.

The behaviour of some N,N'-disubstituted hexahydropyrimidines, a class of naturally occurring compounds of biological and biomedical interest, has been studied in both electron ionization (EI) and electrospray ionization (ESI) modes coupled with collisional experiments (ESI-MSn). In both techniques, the [M-H]+ ions are highly abundant, even if their formation is generated by two different mechanisms, i.e. H. loss from the M+. species in the case of EI and hydride (H-) abstraction from the molecules in the case of ESI. Furthermore, due to the low, step-by-step internal energy deposition typical of collisional experiments performed in an ion trap mass spectrometer, different fragment ions were observed in EI and ESI-MSn collisions. In both cases, the ions can be related to the original structure and allow us to identify the positions in which the different substituents are present.

(1)H- and (13)C-NMR analysis of a series of 1,2-diaryl-1H-4,5-dihydroimidazoles.

An analysis of the (1)H- and (13)C-NMR spectra of a series of 1,2-diaryl-1H-4,5-dihydroimidazoles and comparisons with 4,5-dihydroimidazoles having different substitution patterns are presented. The influence of different 1-aryl and 2-aryl group substituents on spectroscopic parameters of the heterocyclic ring and on the contributions of possible mesomeric structures in the system was determined. Spectroscopic features are coherent with the presence of two conjugated systems (Ar(1)-N and Ar(2)-C=N) which compete with the delocalization characteristics of the amidine system.

Spectroscopic and theoretical studies of derivatives of 1,6- and 1,7-naphthyridines.

The solvatochromism in 8-hydroxy-1,6-naphthyridin-5(6H)-one-7-carboxylic acid methyl ester (1), 5-hydroxy-1,7-naphthyridin-8(7H)-one-6-carboxylic acid methyl ester (2), and 4-hydroxy-2-methyl-1(2H)-isoquinolone-3-carboxylic acid methyl ester (3), has been studied in solvents of different polarity and hydrogen bond donor (HBD) and hydrogen bond acceptor (HBA) ability. The relative stabilities of isomers for these naphthyridine derivatives and their interaction with the solvent are reported. Two intramolecular hydrogen-bonded structures contribute to the ground state of compound 1. Temperature effects on the absorption bands were recorded to analyse the possible equilibrium between covalent and zwitterionic forms. The formation of zwitterionic species was observed only in HBD solvents, from which is inferred the solvent assistance in the proton transference. AM1 and PM3 semi-empirical calculations were used in support of the proposed interpretations.