Anti-mycobacterial activities of some cationic and anionic calix[4]arene derivatives

Various polycharged calix[4]arenes were assayed as anti-mycobacterial agents against Mycobacterium tuberculosis, H37Rv strain. The sulfonate, carboxylate and phosphonate anionic species displayed no activity. Cationic derivatives integrating four aminoethyl groups at the upper rim and two 6,6′-dimethyl-2,2′-bipyridyl- or 4,4′-dimethyl-2,2′-bithiazolyl subunits at the lower rim were also found inactive against M. tuberculosis, while the unsubstituded and the 5,5′-dimethyl-2,2′-bipyridyl-analogues exhibited MIC values of 3.2 and 0.8 μM respectively. Introduction of guanidinoethyl groups at the upper rim resulted, except for the 6,6′-dimethyl-2,2′-bipyridyl-derivative, in high anti-mycobacterial activities for the unsubstituted, the 5,5′-dimethyl-2,2′-bipyridyl- and the 4,4′-dimethyl-2,2′-bithiazolyl analogues, with MIC values of 0.8, 0.8 and 1.6 μM, respectively, similar to those of current commercial anti-tuberculosis agents. The five more active substances were also evaluated against the isoniazid-resistant strain MYC5165, resulting in highly interesting micromolar or sub-micromolar MIC and IC50, ca. 4-125 times more active than isoniazid. These preliminary results are attractive for the development of new anti-TB agents.