Designing 1,2,3‐Triazole Derivatives for Targeted Inhibition of Proteolytic and Coagulant Activities in <i>Bothrops Jararaca</i> and <i>Bothrops neuwiedi</i> Snake Venoms

Abstract Snakebites inflict significant injuries on humans and animals, posing a severe global public health challenge due to high mortality and morbidity rates. This study presents results against the venoms of Bothrops jararaca and Bothrops neuwiedi using sixteen synthetic hybrid molecules containing thiophene and triazoles, designated as 6a–h and 7a–h . The compounds were assessed for their ability to inhibit proteolytic and plasma coagulant activities induced by the snake venoms, and their toxicity was analyzed. Most derivatives demonstrated nontoxicity through in silico analysis with the Osiris Property Explorer tool and in vitro cytotoxic hemocompatibility on red blood cells. Notably, only derivative 6e exhibited toxicity to erythrocytes, while 6b , 6d , 7c , and 7f displayed mutagenic, tumorigenic, or adverse effects on the reproductive system. Derivatives 6a , 6c–h , 7c–e , 7g , or 7h effectively inhibited the coagulating activity of B. jararaca venom, while 6a–b , 6d–e , 6h , or 7a–f inhibited coagulation induced by B. neuwiedi venom. All derivatives demonstrated inhibition of the proteolytic activity caused by B. jararaca venom, and derivatives 6a–d and 7e–f inhibited the activity of B. neuwiedi venom. Consequently, these derivatives exhibited varying degrees of efficacy in countering two crucial toxic effects of B. jararaca or B. neuwiedi venoms, suggesting their potential as antivenoms against both species.