Chalcones and flavonoids as anti-tuberculosis agents.

Area of Science:

• Medicinal Chemistry
• Organic Chemistry
• Microbiology

Background:

• Tuberculosis (TB) remains a significant global health challenge, necessitating the development of novel therapeutic agents.
• Existing anti-TB drugs face challenges like drug resistance and toxicity, driving research into alternative chemical scaffolds.
• Flavonoids, chalcones, and their derivatives are known for diverse biological activities, including antimicrobial properties.

Purpose of the Study:

• To synthesize and evaluate a series of flavonoids, chalcones, and chalcone-like compounds for their inhibitory activity against Mycobacterium tuberculosis H37Rv.
• To identify specific structural features that contribute to enhanced anti-TB activity.
• To determine the minimum inhibitory concentrations (MIC) of the most potent compounds.

Main Methods:

• Synthesis of various flavonoid, chalcone, and chalcone-like compounds.
• In vitro screening of compounds for inhibitory activity against Mycobacterium tuberculosis H37Rv at a concentration of 12.5 microg/mL.
• Determination of minimum inhibitory concentrations (MIC) for active compounds.

Main Results:

• Eight compounds exhibited >90% inhibition of Mycobacterium tuberculosis growth at 12.5 microg/mL.
• Chalcones 22 and 37 showed 90% and 92% inhibition, respectively.
• Chalcone-like compounds 48, 49, 50, and 51 demonstrated high inhibition rates (98%, 97%, 96%, and 96%, respectively).
• MIC values for potent compounds ranged from 6.8 to >35.7 microg/mL.
• Hydrophobic and hydrogen-bonding substituents on aromatic rings correlated with increased anti-TB activity.

Conclusions:

• Chalcones and chalcone-like compounds are promising scaffolds for developing new anti-TB agents.
• Structural modifications, including specific substituent patterns, can significantly enhance anti-mycobacterial activity.
• The study provides valuable insights into structure-activity relationships for anti-TB chalcone derivatives.