Mahmoud Motaz Ghulman
Dar Al Thiker school, Jeddah, Makkah, SAUDI ARABIA
Trichomonas vaginalis is a parasite that causes a common, sexually transmitted disease with a worldwide impact. Infection can predispose to HIV infection and other serious health consequences. Purines are essential for all living organisms to the constitute nucleic acids. T. vaginalis lacks de novo purine synthesis and has to salvage it from host. Therefore, salvage pathways should be eminent targets to chemotherapeutic strategies. The project aims to introduce a novel rationally-designed combinational therapy (Dipyridamole, and Allopurinol) targeting purine salvage pathways of T. vaginalis. Growth inhibition assays were performed to evaluate the effect of the novel drugs on a culture of T. vaginalis trophozoites in TYM medium. Dipridamole/allopurinol combination shows almost complete parasite growth inhibition (98.8%) compared to individual drugs (63.6% & 77.3% respectively) and to the traditional drug; metronidazole (67.1%). This dipyridamole/allopurinol inhibitory effect, in culture, is not expected to be reproduced in vivo due to expected poor bioavailability at the infection site as well as high plasma protein binding. The project`s results represent the first ever to raise the concept of targeting purine salvage pathways –in Trichomonas vaginalis- as a possible line of treatment. They pave the road to test the suggested chemotherapeutic regimen on other purine-auxotroph microorganisms. Future work on using nanotechnology-based methods such as nanocapsulation is expected to provide better delivery in biological systems. Awards won at the 2011 ISEF Fourth Award of $500 - Cellular and Molecular Biology - Presented by Intel