The inhibitory activity of anthraquinones against pathogenic protozoa, bacteria, and fungi and the relationship to structure

Authors: Friedman, Mendel; XU, ALEXANDER - Pacific University; LEE, RANI - Pacific University; NGUYEN, DANIEL - Pacific University; PHAN, TINA - Pacific University; HAMADA, SABRINA - Pacific University; PANCHEL, RIMA - Pacific University; Tam, Christina; Kim, Jong Heon; Cheng, Luisa; LAND, KIRKWOOD - Pacific University

Submitted to: Molecules
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/2/2020
Publication Date: 7/7/2020
Citation: Friedman, M., Xu, A., Lee, R., Nguyen, D.N., Phan, T.A., Hamada, S.M., Panchel, R., Tam, C.C., Kim, J., Cheng, L.W., Land, K.M. 2020. The inhibitory activity of anthraquinones against pathogenic protozoa, bacteria, and fungi and the relationship to structure. Molecules. 25(13):3101. https://dx.doi.org/10.3390/molecules25133101.
DOI: https://doi.org/10.3390/molecules25133101

Interpretive Summary: Trichomoniasis is an infection caused by pathogenic protozoan organisms, known as trichomonads, of the genera Trichomonas and Tritrichomonas. In humans, trichomoniasis caused by T. vaginalis is reported to be the most common non-viral sexually transmitted infection in the world. Because of high rates of clinical resistance to the widely used synthetic drug metronidazole, new approaches are needed to complement the available therapeutic treatments. Strains of T. foetus are reported to cause the pathogenesis of trichomonosis in farm animals (cattle, bulls, and pigs) and domestic animals (cats and dogs). In cattle, the disease causes failed pregnancies and because the disease is asymptomatic in bulls reinfection can occur even after the cows are treated. The most cost-effective method to control the disease is often culling the infected animals. In domesticated cats, the disease is transmitted by the oral-fecal route where it infects the gastrointestinal tract, causing persistent diarrhea. As part of an effort to investigate the efficacy of safe food extracts and their bioactive constituents against parasitic trichomonads, we previously reported on the trichomonad-inhibiting properties of tomato and potato glycoalkaloids and of black tea extracts and their biologically active theaflavins against the three trichomoniasis-causing pathogens mentioned earlier. The present study was designed to complement and extend the results by determining the anti-trichomonad properties of seven seven structurally different plant-derived anthraquinones. All of the evaluated test compounds were found to be active against the three parasitic protozoa; emodin also possessed antifungal activity against the yeast pathogen Candida albicans. None of the compounds showed activity against pathogenic foodborne bacteria or nonpathogenic lactobacilli. It seems, the nature and number of substituents on the anthraquinone ring were found to influence the wide-ranging relative potencies as determined from IC50 values. The most active anthraquinone compounds, aloe-emodin and chrysazin for T. vaginalis (human) and chrysazin and aloe-emodin against both the farm and domestic animal trichomonas strains, merit further study to define their ability to ameliorate both trichomoniasis in humans and trichomonosis in farm and domestic animals.

Technical Abstract: Plant-derived anthraquinones were evaluated in cell assays for their inhibitory activities against the parasitic protozoa Trichomonas vaginalis human strain G3 that causes the sexually transmitted disease trichomoniasis in women, Tritrichomonas foetus bovine strain D1 that causes sexually transmitted diseases in farm animals (bulls, cows, and pigs), Tritrichomonas foetus-like strain C1 that causes diarrhea in domestic animals (cats and dogs), and foodborne bacteria and fungi. The anthraquinones assessed for their inhibitory activity were anthraquinone, aloe-emodin (1,8-dihydroxy-3-hydroxymethylanthraquinone), anthrarufin (1, 5-dihydroxyanthraquinone), chrysazin (1,8-dihydroxyanthraquinone), emodin (1,3,8-trihydroxy-6-methylanthraquinone), purpurin (1,2,4-trihydroxyanthraquinone), and rhein (1,8-dihydroxy-3-carboxyanthraquinone). Their activities were determined in terms of IC50 values, defined as the concentration that inhibits 50% of the cells under the test conditions and calculated from linear dose response plots for the parasitic protozoa, and zone of inhibition for bacteria and fungi, respectively. The results show that the different substituents on the anthraquinone ring seem to influence the relative potency. Analysis of the structure-activity relationships in protozoa indicates that the aloe-emodin and chrysazin with the highest activities merit further study for their potential to help treat the diseases in women and domestic and farm animals. Emodin also exhibited antifungal activity against disease-causing Candida albicans. None of the bacteria were inhibited. The described mechanism of action and the additional reported beneficial biological properties of anthraquinones suggest that they have the potential to ameliorate multiple diseases.