SYNTHESIS AND EVALUATION OF ANTIMICROBIAL ACTIVITY OF ACETOPHENONE-HYDRAZONE DERIVATIVES AGAINST RESISTANT MYCOBACTERIA

Abstract

According to the WHO, microbial resistance is among the most urgent global threats with serious health and economic consequences. In 2024, rifampicin-resistant Mycobacterium tuberculosis (Mtb), which is currently one of the ten leading causes of death worldwide, was added to the WHO's list of priority pathogens for which the development of new antibiotics should be prioritized. In parallel, non-tuberculous mycobacteria (NTM), such as M. kansasii, are also on the rise. They often cause severe diseases, particularly lung infections, and frequently exhibit drug resistance.One promising strategy to overcome resistance is rational design and synthesis of new antimicrobial agents. In particular, combining multiple bioactive scaffolds into a single molecule may lead to compounds with enhanced efficacy and broader activity profiles (multi-target drugs).1 This project explores the hybridization of acetophenone and hydrazide derivatives, both of which have demonstrated antimycobacterial activity.2,3These newly synthesized hydrazones were prepared satisfactorily via condensation of ketone with the corresponding hydrazide in methanol, using glacial acetic acid as a catalyst. Two acetophenone derivates, 4’-cyclohexylacetophenone and 4’-piperidinoacetophenone, were chosen.All new prepared compounds were tested against mycobacteria strains by microdilution broth method. The most effective compounds were subsequently modified to enhance their antimicrobial properties.