Aldo Rodrigues da Silva, Ana Cláudia Rodrigues da Silva, Eladio Flores Sanchez, Gabriel Alves Souto de Aquino, Vitor Francisco Ferreira, Sabrina Baptista Ferreira, André Lopes Fuly
(1) Background: Snake bite envenomation is a neglected disease that affects impoverished and rural areas, causing deaths and physical sequelae. (2) Objective: A novel series of eight 1,2,3-triazole compounds, AM50, AM51, AM52, AM53, AM54, AM55, AM56, and AM57, were synthesized and assessed as inhibitors of toxic activities of B. jararacussu venom. Methods: B. jararacussu venom was pre-incubated with each of the compounds and after the coagulant, proteolytic, hemorrhagic, edematogenic, and lethal activities were assessed. The structure of compounds was analyzed by NMR and FT-IR spectroscopy techniques, and toxicity was predicted through OSIRIS and SwissADME. (3) Results: AM56 and AM57 inhibited the plasma coagulant and prevented hemorrhagic activity of the venom. Proteolysis and hemorrhage were inhibited by AM52, AM54, AM55, and AM56 (20-30%), as well as AM50, AM51, and AM57 (30-60%). AM57 fully protected the mice from death caused by venom, and AM50, AM53-AM57 inhibited edema of venom by 10-20%; AM51 and AM52 did not inhibit edema. In silico analysis of compounds revealed satisfactory parameters for drug discovery. (4) Conclusions: 1,2,3-triazole compounds inhibited the major toxic activities of B. jararacussu venom and should be considered as a lead for further investigation as adjunct of antivenom therapeutics.