Usnic acid, a dibenzofuran, was originally isolated from lichens belonging to secondary metabolites, and is well known as an antibiotic, but also endowed with several other interesting properties. Thus the goal of this paper is the design of new usnic acid derivatives and evaluation of their antimicrobial activities. All newly synthesized compounds possess good antibacterial activity with MIC ranging from 1.02-50.93 x 10-2 mmol/ml and MBC from 2.05-70.57 x 10-2 mmol/ml. The most sensitive bacterial species was Staphylococcus aureus, while Pseudomonas aeruginosa and Escherichia coli were the most resistant among ATCC strains, and MRSA was the most resistant among all tested bacteria (ATCC and clinical isolates). Antifungal activity was very strong (MIC 0.35-7.53 x 10-2 mmol/ml and MFC 0.70-15.05 x 10-2 mmol/ml) better than reference compounds and usnic acid itself. The most sensitive fungal species was T viride while P.versicolor var cyclopium.c appeared to be the most resistant one. The results allow us to conclude that the title compounds are good lead compounds for new more active antibacterial drugs. On the other hand these compounds are very promising as antifungals.