Solvent-Free Synthesis, In Vitro and In Silico Studies of Novel Potential 1,3,4-Thiadiazole-Based Molecules against...

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Microbiology

Background:

• 1,3,4-thiadiazoles are a class of heterocyclic compounds with diverse biological activities.
• Developing novel antimicrobial agents is crucial due to rising drug resistance.

Purpose of the Study:

• To synthesize novel 1,3,4-thiadiazole derivatives.
• To evaluate their in vitro antimicrobial and antifungal activities.
• To investigate their binding interactions with microbial enzymes using molecular docking.

Main Methods:

• Synthesis of 1,3,4-thiadiazoles via grinding method at room temperature.
• Structural elucidation using spectral and microanalytical data.
• Antimicrobial screening against Gram-positive and Gram-negative bacteria and fungi.
• Molecular docking against tyrosyl-tRNA synthetase (TyrRS) and N-myristoyl transferase (Nmt).

Main Results:

• Several novel 1,3,4-thiadiazole derivatives were successfully synthesized.
• Compounds 3 and 5 exhibited significant antimicrobial activity against all tested microorganisms.
• Compound 3 showed potent antifungal activity and favorable binding interactions with microbial enzymes.
• Compound 3 displayed the best binding affinity (-9.1 kcal/mol) and hydrogen bonding interactions.

Conclusions:

• Compound 3 is a promising candidate for further development as an antimicrobial agent.
• The synthesized 1,3,4-thiadiazoles show potential for combating microbial infections.
• In silico and in vitro studies support the therapeutic potential of compound 3.