Computer-aided development of dioxonaphthoimidazolium-based derivatives as novel antibiotics against drug-resistant

Antimicrobial resistance is one of the most urgent global health challenges. Tens of thousands of people die from drugresistant
infections worldwide every year, and these infections carry substantial healthcare and socioeconomic costs. Many existing antibiotics, developed decades ago, are rapidly losing efficacy, and the clinical pipeline lacks new chemical classes capable of overcoming evolving resistance mechanisms. The proposed project aims to address this critical gap by using computer-aided design to synthesize and evaluate a new generation of antibacterial agents derived from the functionalized dioxonaphtho[2,3-d]imidazolium pharmacophore. Although dixonaphthoimidazolium based
analogues have recently demonstrated promising activity against drug-resistant pathogens, including methicillin-resistant Staphylococcus aureus and nutrient-starved Mycobacterium tuberculosis, their structure-activity relationships and permeability determinants remain poorly understood, particularly with regard to Gram-negative
bacteria. This project's central objective is to develop functionalized dioxonaphthoimidazolium-based derivatives with tailored substituents at the N1 and N3 positions to enhance membrane permeability and antibacterial potency. This project combines complementary expertise in chemoinformatics-driven molecular design from Gdansk University of Technology and advanced organic synthesis and biological evaluation from National Taipei University of Technology.