Improving the Potency of <i>N</i>-Aryl-2,5-dimethylpyrroles against Multidrug-Resistant and Intracellular Mycobacteria.
Touitou M, Manetti F, Ribeiro CM, Pavan FR, Scalacci N, Zrebna K, Begum N, Semenya D, Gupta A, Bhakta S, McHugh TD, Senderowitz H, Kyriazi M, Castagnolo D.
A series of <i>N</i>-phenyl-2,5-dimethylpyrrole derivatives, designed as hybrids of the antitubercular agents BM212 and SQ109, have been synthesized and evaluated against susceptible and drug-resistant mycobacteria strains. Compound <b>5d</b>, bearing a cyclohexylmethylene side chain, showed high potency against <i>M. tuberculosis</i> including MDR-TB strains at submicromolar concentrations. The new compound shows bacteriostatic activity and low toxicity and proved to be effective against intracellular mycobacteria too, showing an activity profile similar to isoniazid.