In vitro evaluation of Nucleoside analogs on protozoal pathogens Trichomonas vaginalis and Tritrichomonas foetus

Trichomoniasis, the most common non-viral STD, is caused by the protozoan Trichomonas vaginalis. The only current FDA approved treatment for human trichomoniasis is metronidazole. However, the treatment often causes nausea and diarrhea in addition to the emergence of resistant strains. Tritrichomonas foetus, a closely related protozoan parasite, often causes infertility and spontaneous abortion in cattle. There is no current approved treatment for animals infected. Therefore, the identification for potential molecule can serve as the basis for drug discovery or better treatment for both the animal parasites and human parasite. We carried out a structure activity analysis of a series of adenosine and 7-deazaadenosine analogues against the human protozoan pathogen Trichomonas vaginalis and veterinary protozoal pathogen Tritrichomonas foetus. Compounds 28 and 29 of the library of arabino-fluoroadenosine scaffold are found to be the most potent inhibitors of T. vaginalis growth. Compounds 28 and 29 completely inhibited T. vaginalis growth at 50 μM concentrations with IC50 11.35 μM and 4.132 μM, respectively. In addition, compounds 1, 9, 7, 2, 3, and 8 all exhibited potent activity with 2 demonstrating the lowest IC50. The most potent compounds against the T. foetus were found to be the arabino derivatives, some of which are also potent inhibitors of Sadenosylhomocysteine hydrolase of Trichomonas vaginalis. The 9-[2-deoxy-2-azido β, D-arabinofuranosyl) adenine was found to completely inhibit T. foetus at 10 μM concentrations with IC50 5 μM. Of the purine modified antibiotics tested, toyocamycin and formycin inhibited T. foetus growth with IC50 of 9.3 μM and 10.3 μM, respectively