167264-91-7Relevant articles and documents
Synthesis, molecular docking and antimalarial activity of phenylalanine-glycine dipeptide bearing sulphonamide moiety
Ali, Rafat.,Aronimo, Babatunde. S.,Ezugwu, James. A.,Ibeji, Collins. U.,Okoro, Uchechukwu. C.,Ugwu, David. I.
, (2021/08/10)
Ten novel phenylalanine-glycine dipeptide sulphonamide conjugate were synthesized and characterized using 1HNMR, 13CNMR, FTIR and HRMS spectroscopic techniques. The in silico studies predicted better interactions of compounds with target protein residues and a higher dock score in comparison with standard drugs. The in vivo antimalarial study, hematological study, liver and kidney function test were evaluated on the synthesized compounds. Compounds 7h, 7i and 7j inhibited the parasite by 34.5–60.2% on day 4 of after-treatment exposure. Compound 7j inhibited the multiplication of the parasite by 60.2% on day 4 of after-treatment which was comparable with that of the standard drug with 68.8% inhibition at same day of after-treatment exposure.
Discovery of Potent, Reversible, and Competitive Cruzain Inhibitors with Trypanocidal Activity: A Structure-Based Drug Design Approach
De Souza, Mariana L.,De Oliveira Rezende Junior, Celso,Ferreira, Rafaela S.,Espinoza Chávez, Rocio Marisol,Ferreira, Leonardo L. G.,Slafer, Brian W.,Magalh?es, Luma G.,Krogh, Renata,Oliva, Glaucius,Cruz, Fabio Cardoso,Dias, Luiz Carlos,Andricopulo, Adriano D.
, p. 1028 - 1041 (2019/12/27)
A virtual screening conducted with nearly 4?000?000 compounds from lead-like and fragment-like subsets enabled the identification of a small-molecule inhibitor (1) of the Trypanosoma cruzi cruzain enzyme, a validated drug target for Chagas disease. Subsequent comprehensive structure-based drug design and structure-activity relationship studies led to the discovery of carbamoyl imidazoles as potent, reversible, and competitive cruzain inhibitors. The most potent carbamoyl imidazole inhibitor (45) exhibited high affinity with a Ki value of 20 nM, presenting both in vitro and in vivo activity against T. cruzi. Furthermore, the most promising compounds reduced parasite burden in vivo and showed no toxicity at a dose of 100 mg/kg. These carbamoyl imidazoles are structurally attractive, nonpeptidic, and easy to prepare and synthetically modify. Finally, these results further advance our understanding of the noncovalent mode of inhibition of this pharmaceutically relevant enzyme, building strong foundations for drug discovery efforts.
