N-benzylsalicylthioamides: highly active potential antituberculotics.

Area of Science:

• Medicinal Chemistry
• Microbiology
• Computational Chemistry

Background:

• Tuberculosis (TB) remains a significant global health challenge, exacerbated by the rise of drug-resistant strains.
• There is a continuous need for novel antimycobacterial agents with improved efficacy and safety profiles.

Purpose of the Study:

• To synthesize and evaluate a new series of N-benzylsalicylthioamide derivatives for antimycobacterial activity.
• To explore the structure-activity relationships (SAR) of these compounds against various mycobacterial species.

Main Methods:

• Synthesis of 29 N-benzylsalicylthioamide derivatives.
• In-vitro testing of synthesized compounds against Mycobacterium tuberculosis, Mycobacterium kansasii, and Mycobacterium avium.
• Quantitative structure-activity relationship (QSAR) analysis to correlate chemical structure with biological activity.

Main Results:

• Several synthesized compounds exhibited significant in-vitro antimycobacterial activity.
• Activity was positively correlated with lipophilicity and the electron-donating effect of substituents in the acyl moiety.
• Activity was negatively correlated with the electrophilic superdelocalizability of the molecules.
• The most potent compounds demonstrated higher activity than isoniazid (INH) and were effective against INH-resistant mycobacterial strains.

Conclusions:

• N-benzylsalicylthioamide derivatives represent a promising class of compounds for the development of new anti-TB drugs.
• QSAR analysis provides valuable insights for the rational design of more potent antimycobacterial agents.
• The identified compounds offer potential therapeutic options for drug-susceptible and drug-resistant tuberculosis infections.