Antivenom Effects of 1,2,3-Triazoles againstBothrops jararacaandLachesis mutaSnakes

Abstract

Snake venoms are complex mixtures of proteins of both enzymes and nonenzymes, which are responsible for producing several biological effects. Human envenomation by snake bites particularly those of the viperid family induces a complex pathophysiological picture characterized by spectacular changes in hemostasis and frequently hemorrhage is also seen. The present work reports the ability of six of a series of 1,2,3-triazole derivatives to inhibit some pharmacological effects caused by the venoms of Bothrops jararaca and Lachesis muta. In vitro assays showed that these compounds were impaired in a concentration-dependent manner, the fibrinogen or plasma clotting, hemolysis, and proteolysis produced by both venoms. Moreover, these compounds inhibited biological effects in vivo as well. Mice treated with these compounds were fully protected from hemorrhagic lesions caused by such venoms. But, only the B. jararaca edema-inducing activity was neutralized by the triazoles. So the inhibitory effect of triazoles derivatives against some in vitro and in vivo biological assays of snake venoms points to promising aspects that may indicate them as molecular models to improve the production of effective antivenom or to complement antivenom neutralization, especially the local pathological effects, which are partially neutralized by antivenoms.

Anti-hemorrhagic effect of hydro-alcoholic extract of the leaves of Mikania glomerata in lesions induced by Bothrops jararaca venom in rats

“…The Bothrops genus (family Viperidae) encloses some of the most remarkable species from the medical point of view, since it contributes 73.1% of the ophidian annual accidents which occur in Brazil [1][2][3] .…”

Synthesis, characterization and utilization of a new series of 1,2,3-triazole derivatives to neutralize some toxic activities of Bothrops jararaca snake venom

“…( Our group has previously tested triazoles with different chemical groups against the toxic activities of snake venoms. Domingos et al, (2013) tested six triazole derivatives, and they inhibited the coagulant, proteolytic, hemolytic, hemorrhagic, and edematogenic activities of B. jararaca and Lachesis muta venom, regardless of the substituent attached to the triazole ring. Thus, these data corroborate the potential use of triazoles as antivenoms, since they are stable, have a simple and cheap route of synthesis, and are devoid of toxicity.…”

“…Antivenom is effective in preventing death of victims, but, by contrast, it has some drawbacks: low capability to inhibit local effects of venoms, low stability in liquid form, thermolability, high cost of production, and in some cases, antivenom may produce fever or anaphylactic reactions (Williams et al, 2019b;Gómez-Betancur et al, 2019). Thus, the limited efficacy of antivenoms may justify alternative therapies, which include monoclonal antibodies, aptamers, molecules derived from sponges, seaweed, plants or organic synthesis (Williams et al, 2019b;Campos et al, 2020;Ascoët, Ward, 2020;Faioli et al, 2013;da Silva et al, 2017;de Oliveira et al, 2016;Domingos et al, 2013;Pucca et al, 2019). Triazole is a five-membered heterocyclic compound containing three nitrogen atoms, with two isomeric forms (1,2,3-triazole or 1,2,4-triazole).…”

“…In addition, some molecules containing the triazole nucleus have been used as a core structural component of drugs (Kharb, Sharma, Yar, 2011). Our group has demonstrated the inhibitory potential of triazole derivatives against the toxic activities of the venom of B. jararaca and L. muta snakes (Domingos et al, 2013). Therefore, we decided to evaluate the effect of eight derivatives of a new series of 1,2,3-triazole against some toxic activities of B. jararaca venom.…”

1,2,3-Triazole Nucleus as a Versatile Tool for the Obtainment of Novel Biologically Active Compounds: an Overview

“…Dificultando ainda mais, em geral, menos de 0,01 % dos protótipos de compostos bioativos sintetizados nos laboratórios têm sucesso nas etapas préclínicas, que compreendem os ensaios biológicos in vitro realizados após a etapa de síntese, purificação e caracterização. [1][2][3][4][5] Dentro deste contexto, sintetizar compostos contendo um núcleo 1,2,3-triazólico em sua estrutura molecular (1-13) é uma estratégia eficiente e amplamente explorada [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] para obtenção de novas moléculas com variadas atividades biológicas, como: antiviral [26][27][28][29] , antídoto 30,31 , antiinflamatória 32 , antibacteriana 33 , antitumoral 34,35 e antimicrobiana 36 (Figura 2). Dentre as vantagens de se incorporar este heterociclo, de origem estritamente sintética, na estrutura molecular do produto planejado destacam-se: (i) podem interagir com diferentes receptores biológicos através de ligações de hidrogênio e/ou interações hidrofóbicas do tipo π-stacking com resíduos de aminoácidos como a fenilalanina; (ii) podem atuar como elos de união entre duas moléculas (linkers), possibilitando a obtenção de compostos híbridos; (iii) podem ser introduzidos na estrutura molecular de um composto como um bioisóstero, por exemplo, na substituição de uma função amida, a fim de evitar reações de hidrólise.…”