New bithiazolyl hydrazones: Novel synthesis, characterization and antitubercular evaluation

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Antimicrobial Agents

Background:

• Tuberculosis (TB) remains a major global health challenge, necessitating the development of novel therapeutic agents.
• Bithiazolyl hydrazones represent a class of heterocyclic compounds with potential biological activities.
• Existing treatments face challenges like drug resistance and side effects, driving the search for new drugs.

Purpose of the Study:

• To synthesize novel bithiazolyl hydrazones using a one-pot cyclocondensation reaction.
• To evaluate the synthesized compounds for their in vitro antitubercular and antibacterial activities.
• To investigate the potential of these compounds as new antimicrobial agents.

Main Methods:

• One-pot cyclocondensation of 5-acyl thiazoles, thiosemicarbazide, and substituted phenacyl chlorides in ionic liquid (DIPEAc).
• In vitro antitubercular activity screening against Mycobacterium tuberculosis.
• In vitro antibacterial activity screening against various bacterial strains.
• Cytotoxicity evaluation.
• Molecular docking studies to predict binding interactions.

Main Results:

• Successfully synthesized a series of new bithiazolyl hydrazones (compounds 6a-l).
• Compounds 3b, 6a, 6b, 6d, 6e, 6f, 6g, and 6l demonstrated notable antitubercular activity compared to Rifampicin, with acceptable cytotoxicity.
• Compounds 6j and 6k exhibited significant antibacterial activity.
• Molecular docking results correlated well with the observed in vitro antitubercular activity.

Conclusions:

• The synthesized bithiazolyl hydrazones are promising candidates for developing new antitubercular and antibacterial drugs.
• The one-pot synthesis in ionic liquid offers an efficient route to these novel compounds.
• Further investigation is warranted to optimize these compounds for therapeutic applications.