Guanidinium compounds with sub-micromolar activities against Mycobacterium tuberculosis. Synthesis, characterization and biological evaluations.

Seven polycharged species, incorporating 1, 2, 3, 4 and 6 guanidine arms organized around a benzene core were synthesized and assayed as anti-mycobacterial agents against Mycobacterium tuberculosis. They display MIC values comprised between 25 and 12.5 μM (close to ethambutol EMB) for the mono- and the hexa-substituted derivatives, and 0.8 μM (close to isoniazid and streptomycin) for the tri-substituted derivative. The three bi- and the tetra-substituted analogs displayed MIC values of ca. 6.5-3.0 μM. The latter were also evaluated against the isoniazid-resistant MYC5165 strain, resulting in highly interesting micromolar or sub-micromolar MIC, ca. 4-125 times more active than isoniazid. These preliminary results are attractive for the development of new anti-TB agents.