Novel 1,2,3-triazoles as Inhibitors of the Toxic Effects of the Venom of the Snake Lachesis muta muta

Abstract

Aims: Snakebites are a health problem worldwide that produce pathological symptoms, as hemorrhage, tissue necrosis, blood coagulation disorder, edema, and death. Although serum therapy protects victims of death, it does not prevent amputation of the affected limb. Thus, alternative treatments deserve attention. Background: To test a new series of twelve dissubstituted triazoles TRI 02, TRI 03, TRI 04, TRI 05, TRI 07, TRI 08, TRI 09, TRI 11, TRI 14, TRI 16, TRI 17 or TRI 18 against hemorrhagic, edematogenic, hemolytic, coagulant or proteolytic activities of L. muta venom. Objective: To test a new series of twelve dissubstituted triazoles TRI 02, TRI 03, TRI 04, TRI 05, TRI 07, TRI 08, TRI 09, TRI 11, TRI 14, TRI 16, TRI 17 or TRI 18 against hemorrhagic, edematogenic, hemolytic, coagulant or proteolytic activities of L. muta venom. Method: The derivatives were incubated with L. muta venom (protocol of incubation), and, then, the toxic activities were performed. Moreover, L. muta venom was injected before (protocol of treatment) or after (protocol of prevention) the derivatives. Result: Most of the derivatives inhibited proteolytic or hemolytic, but only TRI 17 inhibited coagulation activity of L. muta venom. The derivatives TRI 03, TRI 05, TRI 07, TRI 14 or TRI 17 inhibited hemorrhage; while TRI 07, TRI 08 or TRI 16 inhibited edema. The derivatives TRI 03, TRI 07 or TRI 11 inhibited hemorrhage even if they were given after or before L. muta venom. According to in silico, the derivatives TRI 03, TRI 04, TRI 07, TRI 08, TRI 09, TRI 16, TRI 17 or TRI 18 were not toxic. The derivatives did not violate the Lipinksi´s rule of five. Conclusion: Thus, these new series of triazoles may help the development of molecules able to improve the treatment of L. muta envenoming. other: none