The spread of antibiotic-resistant microorganisms poses a major global health threat, increasing the risk of complications and mortality associated with infections. It is estimated that by 2050, deaths from resistant bacteria could reach 1.9 million annually, underscoring the urgent need for novel antibacterial agents capable of overcoming resistance mechanisms. Isonicotinic acid hydrazide (INH), a first-line drug for tuberculosis, acts by inhibiting the InhA enzyme and disrupting mycolic acid biosynthesis, which justifies its fragment as a rational structural component for new derivatives. Chalcone-based compounds exhibit multiple mechanisms of action, including enzyme inhibition, membrane destabilisation, efflux pump suppression, and biofilm inhibition, and have demonstrated activity against Staphylococcus aureus, including methicillin-resistant strains (MRSA). This project aims to synthesise hybrid molecules combining isonicotinic hydrazide and chalcone fragments, characterise their structures, and evaluate antibacterial activity, contributing to innovative therapeutic strategies against antibiotic resistance.
Project results:
The project aims to create a library of novel isonicotinic acid hydrazide derivatives containing thiazole and chalcone moieties, to investigate their structure-activity relationships (SAR) and possible mechanisms of action, as well as to optimise lipophilicity and pharmacokinetic properties using experimental and computational methods. Computational modelling will include SAR analysis, ligand and protein affinity assessment, and pharmacophore modelling to predict interactions with biological targets and select the most promising candidates prior to synthesis. This strategy will allow for rational experimental planning and reduce the amount of practical work.
Period of project implementation: 2026-07-01 - 2026-08-31
Project coordinator: Kaunas University of Technology
