Antimycobacterial activity and preliminary characterization of a 2-thio-malonylurea derivative against clinically relevant Mycobacterium species

Mycobacterial infections remain a significant public health concern, particularly those caused by environmental and non-tuberculous mycobacteria (NTM). This study aimed to design, synthesize 2–11 , and evaluate 2-thio-malonylurea compounds as potential antimycobacterial agents. The synthesized compounds were subjected to in silico evaluation using SwissADME and screened for antibacterial activity against Gram-positive bacteria. The most active derivative was subsequently evaluated against clinically relevant Mycobacterium species, and its effects on mycobacterial morphology and mammalian cell viability were investigated by scanning electron microscopy (SEM) and cytotoxicity assays, respectively. LQFM238 ( 7 ) exhibited the strongest antibacterial activity among the compounds tested, showing activity against both Gram-positive bacterial species, with MIC values of 125 µg/mL against S. aureus and 250 µg/mL against E. faecalis . It showed antimycobacterial activity against M. tuberculosis H37Ra (MIC 62.5 µg/mL), M. avium (MIC 25 µg/mL), M. abscessus subsp. bolletii (MIC 50 µg/mL), and M. abscessus subsp. abscessus (MIC 50 µg/mL), whereas MIC value ≥ 100 µg/mL were observed for M. intracellulare . SEM revealed marked morphological alterations after exposure to 500 µg/mL for 24 h. Cytotoxic effects were observed only at 41.67 µg/mL, with selectivity indices of 4.15 for M. avium and 2.08 for both M. abscessus strains. LQFM238 ( 7 ) demonstrated promising antimycobacterial activity, particularly against M. avium and clinical M. abscessus strains.