Screening of anti-nosemosis active compounds based on the structure-activity correlation

Abstract Nosema ceranae infection in Apis mellifera acts as a virulent pathogenic factor of honeybee colony collapse. Fumagillin is the only effective antimicrobial agent currently used against the microsporidial parasite N. ceranae. However, the toxicity of fumagillin is a concern. Therefore, in the present study, the screening of potent alternatives for fumagillin was performed for a total of 21 compounds, including 15 phenolics and 6 monoterpenes, based on their structure-activity correlation. The anti-nosemosis activity of each compound was determined by the relative inhibition level against the expression of the N. ceranae virulence factor encoding the polar tube protein 3 (ptp3) mRNA of the ptp3 gene. Each compound was preliminarily evaluated at 100 and 200 µM treatment concentrations. Then, the activity of 12 compounds showing activity at 200 µM was additionally determined at 40 µM, a concentration generally used in apiaries. At this concentration, gallol (benzene-1,2,3-triol) and 3-pentylcatechol (PC) showed higher activities than fumagillin, and 4-pentylgallol (PG) exhibited activity at a similar level to fumagillin. All three compounds selected in this study were low-molecular-weight phenolics. Among them, PC and PG, chemically synthesized compounds, commonly possess a hydrocarbon side chain of the pentyl group (-C5H11) in catechol and gallol, respectively. That is, the three treatment compounds were selected as potential beneficial alternatives for fumagillin and were markedly different from fumagillin in terms of their chemical structure. These results may trigger further extensive research on the biological mechanism for the prevention of nosemosis.