Activity against Mycobacterium tuberculosis with concomitant induction of cellular immune responses by a tetraaza-macrocycle with acetate pendant arms

Autor: Rita Delgado, Judite Costa, Suzana David, Diane J. Ordway, Maria-Jorge Arroz
Rok vydání: 2001
Předmět:
Zdroj: Research in Microbiology. 152:569-576
ISSN: 0923-2508
DOI: 10.1016/s0923-2508(01)01231-1
Popis: The novel tetraaza-macrocyclic compound 3,7,11-tris(carboxymethyl)-3,7,11,17-tetraaza-bicyclo[11.3.1]hep tadeca-1(17),13,15-triene, abbreviated as ac 3 py14, was investigated for its activity against Mycobacterium tuberculosis and for induction of protective cellular immune responses. Perspective results show that ac 3 py14 and its Fe 3+ 1:1 complex, [Fe(ac 3 py14)], inhibited radiometric growth of several strains of M. tuberculosis . Inhibition with 25 μg/mL varied from 99% for H37Rv to 80% and above for multiple drug-resistant clinical isolates. The capacity of ac 3 py14 to elicit a beneficial immune response without cellular apoptosis was assessed and compared to the effects of virulent M. tuberculosis . The present study produces evidence that after stimulation with ac 3 py14 there was significant production of interferon gamma (IFN- γ ), whereas the production of interleukin-5 (IL-5) remained low, and there was development of a memory population (CD45RO). The level of binding of Annexin V, a marker of apoptosis, was not sufficient to result in toxic effects toward αβ and γδ T cells and CD14 + macrophages. This preliminary study is the first report of a compound that simultaneously exerts an inhibitory effect against M. tuberculosis and induces factors associated with protective immune responses.
Databáze: OpenAIRE