Trichomoniasis is one of the most common sexually transmitted diseases caused by the protozoan Trichomonas vaginalis. This protozoan is not able to synthesize purine and pyrimidine rings, hence it scaveages nucleosides from the host cells, and obtains nucleobases through salvage pathway enzymes. The purine-specific adenosine/guanosine nucleoside ribohydrolase (AGNH) enzyme is one of the enzymes the parasite uses to obtain the nucleobases. Therefore the inhibition of AGNH represents a focus for research regarding novel treatment. The goal is to synthesize a molecule with a sub micromolar IC50 value that can inhibit AGNH, hence preventing T. vaginalis from growing. Preliminary results had shown that analogs of quinazolin-2-amine inhibited AGNH with IC50 values of 6.5 μM, 6.8 μM and 46 μM. The structures of the quinazolin-2-amine analogs, were combined with the pyrimidine ring structure of adenine and guanine to design analogs. Primary amines were reacted with 4-chloroquinazoline and 2,4-dichloroquinazoline to obtain N-substituted quinazoline-4-amine and N-substituted 2-chloroquinazoline-4-amine derivatives respectively. N-substituted 2-chloroquinazoline-4-amines were further reacted with another primary amine resulting in N 2,N 4 -disubstituted quinazoline-2,4-diamine derivatives. The results from the IC50 values showed that the products with the presence of amine groups at the 2 and 4 positions better inhibited AGNH.

Synthesis of N-substituted quinazoline-4-amine and N 2,N 4 -disubstituted quinazoline-2,4-diamine derivatives as adenosine/guanosine nucleoside ribohydrolase inhibitors in trichomoniasis

Where thousands of chemistry professionals meet to share ideas and advance scientific and technical knowledge. Spring 2023 abstracts, posters, and presentations will launch at the end of March.

ACS Spring 2023

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.