A set of structurally diverse N-amino δ-lactams decorated with a 5-nitro-2-furyl moiety was synthesized using isocyanide-based multicomponent chemistry and evaluated for antibacterial activity. Three compounds displayed a selective and potent (MIC 22-33 μM) inhibition of M. tuberculosis H₃₇Rv strain growth, while other Gram-positive (MRSA and E. faecium) or Gram-negative (E. coli, P. aeruginosa, A. baumannii, K. pneumoniae) pathogens were not affected. The compounds also displayed moderate-low cytotoxicity, as demonstrated in cell line viability assays. Several multidrug- and poly-resistant patient-derived M. tuberculosis strains were found to be susceptible to treatment with these compounds. The three most potent compounds share a significant structural similarity which provides a basis for further scaffold-hopping analog design.