Dual Agents: Fungal Macrocidins and Synthetic Analogues with Herbicidal and Antibiofilm Activities.

Eight analogues of the bioherbicides macrocidin A () and Z () with structural variance in the size of the macrocycle, its - or -cyclophane character, and its functional groups were synthesized on two modular routes and tested for herbicidal, antibiotic, and antibiofilm activities. Apart from the lead compounds and , the structurally simplified dihydromacrocidin Z () and normacrocidin Z () showed high herbicidal activity in either thistles, dandelions or in both. The derivatives , , and dibromide also inhibited the growth of biofilms by ca 70% when applied at subtoxic concentrations as low as ca 20 µM, which are unlikely to induce bacterial resistance. They also led to the dispersion of preformed biofilms of , exceeding a similar effect by microporenic acid A, a known biofilm inhibitor. Compounds and showed no noticeable cytotoxicity against human cancer and endothelial cells at concentrations below 50 µM, making them conceivable candidates for application as anti-biofilm agents in a medicinal context.