A novel chemotherapeutic combination for Trichomonas vaginalis targeting purine salvage pathways of the parasite.
A novel combination of chemotherapy (Dipyridamole/Allopurinol) targeting the possible purine salvage mechanisms of Trichomonas vaginalis was used in this study. The possible effect of these drugs either individually or in combination, on the multiplication of T. vaginalis in modified TYM axenic culture, was assessed on 24 hours intervals. The combination of both drugs at concentrations of 5 microM and 10 microM each showed a potent lethal effect on the parasite and an almost complete inhibition of parasite multiplication in culture. Each drug, individually, has a significant but partial inhibitory effect on parasite multiplication. Surprisingly, allopurinol, a competitive inhibitor of hypoxanthine, a nucleobase that is not salvaged by the parasite, showed a more potent inhibitory effect on parasite multiplication than dipyridamole, a specific inhibitor of the transport of adenosine, a favored nucleoside to T. vaginalis. However, the inhibitory effect of either drugs declines with time in contrast with that of the combination of both drugs which continues throughout all time points of the experiment. These results prove that a combination of dipyridamole and allopurinol could be useful, not only in the treatment of trichomoniasis, but also in other parasites that are unable of de novo purine synthesis.
Afifi
M A
MA
Departments of Parasitology, Faculties of Medicine, El Minia, Ain Shams and El Menoufiya Universities, Egypt.
el-Wakil
H S
HS
Abdel-Ghaffar
M M
MM
D000493:Allopurinol / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage / Q000494:pharmacology; D004176:Dipyridamole / Q000008:administration & dosage / Q000494:pharmacology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D011687:Purines / Q000378:metabolism*; D014247:Trichomonas Vaginitis / Q000188:drug therapy; D014246:Trichomonas vaginalis / Q000187:drug effects* / Q000378:metabolism*
D000963:Antimetabolites; D011687:Purines; D000493:Allopurinol; D004176:Dipyridamole