Synthesis and Biological Evaluation of (+)-Usnic Acid Derivatives as Potential Anti- Agents.

Six series of (+)-usnic acid derivatives were synthesized. The IC values of these compounds were determined in infected HeLa cells (μM) and in HeLa cells (μM), and their selectivity indexes (SI) were calculated. In vitro, most of the derivatives tested in this study exhibited more anti activity than that of the parent compound (+)-usnic acid and the positive control drugs. Among these derivatives, methyl ()-(1-(6-acetyl-7,9-dihydroxy-8,9b-dimethyl-1,3-dioxo-3,9b-dihydrodibenzo[,]furan-2(1)-ylidene)ethyl)phenylalaninate () showed the most effective anti- activity (selectivity >2.77). In comparison with the clinically used positive control drugs sulfadiazine (selectivity 1.15), pyrimethamine (selectivity 0.89), spiramycin (selectivity 0.72), and the lead compound (+)-usnic acid (selectivity 0.96), showed better results in vitro. Furthermore, and ()-6-acetyl-7,9-dihydroxy-8,9b-dimethyl-2-(1-(quinolin-6-ylamino)ethylidene)dibenzo[,]furan-1,3(2,9b)-dione () had greater inhibitory effects on (inhibition rates 76.0% and 64.6%) in vivo in comparison to spiramycin (inhibition rate 55.2%); in the peritoneal cavity of mice, the number of tachyzoites was significantly reduced ( < 0.001) in vivo. Additionally, some biochemical parameters were measured and spleen indexes were comprehensively evaluated, and the results indicated that mice treated with both compound and compound showed reduced hepatotoxicity and significantly enhanced antioxidative effects in comparison to the normal group. Granuloma and cyst formation were effected by the inhibition of compound and compound in liver sections. Overall, these results indicated that and for use as anti- agents are promising lead compounds.