Synthesis, in vitro antibacterial and antiprotozoan evaluation of 4,7-disubstituted quinolines

Abstract

The rise of antimicrobial resistance has become a critical global health threat, rendering current treatments ineffective against multidrug-resistant pathogens. This issue is further compounded by the limited availability of effective drugs for neglected diseases and their associated toxicity and inadequate drug-like properties. In light of these challenges, the development of novel compounds and therapeutic strategies has become an urgent necessity in the fight against antimicrobial resistance. Among the diseases with limited treatment options, human African trypanosomiasis (HAT),commonly known as sleeping sickness, stands out as a particularly challenging and lethal protozoal disease. HAT is caused by Trypanosoma parasites transmitted through tsetse flies. The currently approved drugs for HAT management suffer from poor drug-like properties and severe side effects. Similarly, African animal trypanosomiasis, a form of trypanosomiasis affecting animals, presents treatment challenges due to limited available drugs and concerns over toxicity. Leishmaniasis, caused by Leishmania parasites transmitted by sandflies, manifests in three main clinical presentations. This disease is prevalent in regions with poor healthcare access, resulting in limited diagnosis, treatment, and prognosis. Although several drugs are used to combat leishmaniasis, the currently most effective treatment options are marred by severe side effects, poor drug-like properties, and emerging drug resistance. ESKAPE pathogens, including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp., are highly resistant to antimicrobials and contribute significantly to mortality rates. These pathogens pose a major concern, particularly in healthcare settings and among immunocompromised patients. Quinolines have demonstrated broad-spectrum biological activities. Aminochalcone, another compound class, has exhibited antimicrobial properties and various other desired pharmacological properties. Nitro-containing carbocycles are increasingly gaining attention from researchers due to their antimicrobial properties. The electron-attracting characteristics of the nitro group contribute to redox reactions in cells, leading to the demise of microorganisms. Aromatic nitro compounds, including fexinidazole and benznidazole, have demonstrated efficacy against protozoans and several bacterial pathogens.