Exploiting the Property of a New Series of 1,2,3-Triazole Compounds as Inhibitors of In Vivo and In Vitro Toxic Effects Caused by Bothrops jararacussu Snake Venom.

(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.