Design, synthesis and effect of triazole derivatives against some toxic activities of Bothrops jararaca venom

According to the World Health Organization, snakebite envenoming is a neglected disease that affects around 5.4 million people worldwide each year. In Brazil, in 2019 there were 29,000 cases of accidents, with 104 deaths. The genus Bothrops was responsible for 90% of reported envenomations, mainly the species B. jararaca. The current therapy is performed with an intravenous injection of antivenom, be it monovalent or polyvalent. However, this treatment has high manufacturing costs, may induce side effects, and it does not effectively neutralize tissue necrosis. The latter issue may lead to deformity or amputation of the affected limb. Therefore, new treatments are needed to aid or improve the efficacy of antivenoms. In this study, nine triazole compounds (AM11–AM19) were chemically synthesized, characterized using infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy analyses, and tested against some in vitro (hemolysis, coagulation, and proteolysis) and in vivo (hemorrhaging, lethal, and edema) activities of B. jararaca venom. Each compound was incubated with B. jararaca venom (incubation protocol) or injected after the venom (treatment protocol), and then, biological assays were performed. As a result, all the compounds inhibited the toxic activities of B. jararaca venom with different potencies in the incubation protocol, while the compound AM13 inhibited hemorrhaging in the treatment protocol. In addition, the compounds were devoid of toxicity, as shown through admetSAR analysis or in vitro cytotoxicity test. Thus, these compounds may be an important tool for the development of antivenom molecules to improve serum therapy for recovering patients envenomed by B. jararaca venom.