A comprehensive insight into naphthalimides as novel structural skeleton of multitargeting promising antibiotics

The globally growing antimicrobial resistance seriously threatens human health, increasing efforts have been devoting to the development of novel antibiotics. Naphthalimides contain a special skeleton of cyclic double imides and the naphthalene framework, this unique structure can exert multitargeting abilities which are helpful to overcome the escalating issue of resistance. Therefore, research in connection with the development of naphthalimides as novel antimicrobial agents is becoming progressively active. It has been revealed that naphthalimides as novel structural skeleton of multitargeting promising antibiotics could not only target DNAs and enzymes, disturb membrane, produce reactive oxygen species, etc. suggesting the multitargeting actions which do not induce resistance, but also show a broad antimicrobial spectrum with safety profile and pharmacokinetic characteristics, implying large potential as a new type of antibiotics via continuous efforts toward antimicrobial naphthalimides. This review presents naphthalimides as a new type of potential antimicrobial agents and discusses rational design strategies, structure-activity relationships, and mechanisms of action, with a comprehensive view to providing a new insight for in the rational design of efficient, broad-spectrum, and low-toxic naphthalimide antibiotics.