Pyridinium Modified Anthracenes and Their Endoperoxides Provide a Tunable Scaffold with Activity against Gram-Positive and Gram-Negative Bacteria.

Due to the emergence of multidrug resistant bacteria, the development of new antibiotics is required. We introduce here asymmetrically modified positively charged bis(methylpyridinium) anthracenes as a novel tunable scaffold, in which the two positive charges can be placed at a defined distance and angle. Our structure-activity relationship reveals that coupling the methylpyridiniums with alkynyl linkers to the central anthracene unit yields antibacterial compounds against a wide range of bacteria, including , , and . Also, different mycobacteria, such as and , are efficiently targeted by these compounds. The antibacterial activity depends on the number of alkynyl linkers and consequently also on the distance of the positive charges in the rigid anthracene scaffold. Additionally, the formation of an anthracene endoperoxide further increases the antibacterial activity, likely due to the release of toxic singlet oxygen that converts the endoperoxide back to the antibacterial anthracene scaffold with half-lives of several hours.