Synthesis and Antibacterial Evaluation of Novel Small-Molecule Antibacterials of a Reduced Acridine Structure in S. aureus Strains Including MRSA

Abstract

Background: The increasing antibacterial drug resistance remains a threat to global health with increasing mortality and morbidity. There is an urgent need to find novel antibacterials and develop alternative strategies to combat the increasing antibacterial drug resistance.

Objective: We aimed to synthesize novel small-molecule antibacterials to evaluate the structuredependent antibacterial compound activities against S. aureus and MRSA.

Methods: Compounds were synthesized by primary N-alkylation to form alkyl acridinium salts that were further functionalized with substituted phenyl residues and finally purified by column chromatography. The antibacterial growth inhibition activity was determined as MIC value.

Results: The substituent effects on the determined antibacterial growth inhibitory properties have been discussed.

Conclusion: The best activities have been found for compounds with methoxy functions, exceeding the activities of reported novel antibacterial peptides. The compounds have also shown antibacterial drug-enhancing effects, which have been manifested as a reduction in the MIC values of the used antibiotics.

Keywords: Drug development; MRSA.; antibacterial activity; enhancers; small molecules; substituent effects.