RESUMEN
Being crucial part of plant-based novel discovery of drug from natural resources, a study was done to explore the antibacterial potential of curcumin mimics in combination with antibiotics against multidrug resistant isolates of Pseudomonas aeruginosa. The best candidate Van D, a curcumin mimics reduced the MIC of tetracycline (TET) up to 16 folds against multidrug resistant clinical isolates. VanD further inhibited the efflux pumps as evident by ethidium bromide efflux and by in-silico docking studies. In another experiment, it was also found that Van D inhibits biofilm synthesis. This derivative kills the KG-P2, an isolate of P. aeruginosa in a time dependent manner, the post-antibiotic effect (PAE) of tetracycline was extended as well as mutant prevention concentration (MPC) of TET was also decreased. In Swiss albino mice, Van D reduced the proinflammatory cytokines concentration. In acute oral toxicity study, this derivative was well tolerated and found to be safe up to 1000 mg/kg dose. To the best of our knowledge, this is the first report on curcumin mimics as synergistic agent via inhibition of efflux pump.
Asunto(s)
Antibacterianos/uso terapéutico , Chalconas/uso terapéutico , Farmacorresistencia Bacteriana/efectos de los fármacos , Animales , Antibacterianos/síntesis química , Antibacterianos/metabolismo , Antibacterianos/toxicidad , Proteínas de la Membrana Bacteriana Externa/metabolismo , Biopelículas/efectos de los fármacos , Chalconas/síntesis química , Chalconas/metabolismo , Chalconas/toxicidad , Curcumina/química , Curcumina/farmacología , Diseño de Fármacos , Sinergismo Farmacológico , Femenino , Masculino , Proteínas de Transporte de Membrana/metabolismo , Ratones Endogámicos BALB C , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Unión Proteica , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/fisiología , Tetraciclina/farmacologíaRESUMEN
Quinoxalines are benzopyrazines containing benzene and pyrazine rings fused together. In the recent past, quinoxalines have attracted Medicinal Chemists considerably for their syntheses and chemistry due to their distinct pharmacological activities. Diverse synthetic protocols have been developed via multicomponent reactions, single pot synthesis and combinatorial approach using efficient catalysts, reagents, and nano-composites etc. Further, the versatility of the quinoxaline core and its reasonable chemical simplicity devise it extremely promising source of bioactive compounds. Therefore, a wide variety of bioactive quinoxalines has been realised as antitumour, antifungal, anti-inflammatory, antimicrobial, and antiviral agents. Already, a few of them are clinical drugs while many more are under various phases of clinical trials. Present review focuses on chemistry and pharmacology (both efficacy and safety) of quinoxalines and also provides some insight in to their structure-activity relationship.