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

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• 作者：David ; Suzana ; Ordway ; Diane ; Arroz ; Maria-Jorge ; Costa ; Judite ; Delgado ; Rita
• 关键词：Mycobacterium tuberculosis ; chemotherapy ; immunotherapy ; macrocyclic compounds
• 刊名：Research in Microbiology
• 出版年：2001
• 期刊代码：75_09232508
• 类别：imm
• 出版时间：July - August, 2001
• 卷：152
• 期：6
• 页码：569-576
• 文件大小：117 K

摘要

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 ac₃py14, was investigated for its activity against Mycobacterium tuberculosis and for induction of protective cellular immune responses. Perspective results show that ac₃py14 and its Fe³⁺ 1:1 complex, [Fe(ac₃py14)], 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 ac₃py14 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 ac₃py14 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.