Azasterol Inhibition and Pharmacokinetic Effects on Thymidylate Synthase-Dihydrofolate Reductase from T. gondii: In Silico Study

Abstract

Toxoplasmosis is a disease that causes health problems and can be found worldwide with a percentage of more than 60%, especially in developing countries such as Indonesia. Pyrimethamine-resistant strains of T. gondii have been found, and it may contribute to reducing therapeutic failure in the future. Azasterol is a synthetic analog of solacongestidine, which can potentially be used as a new anti-toxoplasma drug. Resistance to the anti-toxoplasma drug, Pyrimethamine, makes Azasterol a very profitable discovery as a new anti-toxoplasma drug. This study aimed to determine the inhibitory and pharmacokinetic effects of Azasterol compounds on the development of T. gondii based on in silico studies. This oneshot experimental study analyzed the predicted inhibitory effect of Azasterol on Thymidylate synthasedihydrofolate reductase (TS-DHFR) from T. gondii to observe the pharmacokinetic prediction and toxicity test of the Azasterol compound. Besides, this one-shot experimental study utilized the in silico method. According to the results of molecular docking, Azasterol had an interaction with the TS-DHFR protein in the same binding area as the Pyrimethamine – TS-DHFR and Sulfadiazine – TS-DHFR complexes. Azasterol binding energy was higher than that of Pyrimethamine and Sulfadiazine. Azasterol had a good pharmacokinetic effect and had minimal toxic effects on the body. Key words: In silico, Toxoplasmosis, Azasterol, TS-DHFR.