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Vanillic acid as phospholipase A2 and proteases inhibitor: In vitro and computational analyses
Biotechnology and Applied Biochemistry ( IF 2.8 ) Pub Date : 2020-05-18 , DOI: 10.1002/bab.1943
Pedro H S Cesar 1 , Marcus V Trento 1 , Thais A Sales 2 , Anderson A Simão 1 , Teodorico C Ramalho 2 , Silvana Marcussi 1
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Enzymatic inhibition by natural compounds may represent a valuable adjuvant in snakebite serum therapy. The objective in this work was to evaluate possible in vitro interactions between vanillic acid and enzymes from Bothrops spp. and Crotalus durissus terrificus venoms, and also suggest a theory as how they interact based on molecular docking. Vanillic acid inhibited the phospholipase activity induced by Bothrops alternatus (∼25% inhibition); the caseinolytic activity induced by Bothrops atrox (∼30%), Bothrops jararacussu (∼44%), and C. d. terrificus (∼33%); the fibrinogenolysis induced by B. jararacussu, B. atrox, and C. d. terrificus (100%); the serine protease activity induced by Bothrops moojeni (∼45%) and Bothrops jararaca (∼66%); the hemolytic activity induced by B. moojeni (∼26%); the thrombolysis activity induced by B. atrox (∼30%) and B. jararacussu (∼20%); and the thrombotic activity induced by C. d. terrificus (∼8%). The compound was also capable of delaying the coagulation time in citrated plasma by 60, 35, and 75 Sec, when incubated with B. moojeni, B. atrox, and B. jararaca, respectively. The results obtained expand the possibilities for future pharmaceutical use of vanillic acid, considering the high homology degree among human and snake venom phospholipases A2 and proteases (involved in chronic inflammatory diseases). Also, this compound can be used as adjuvant to improve currently available treatments for ophidism victims.

中文翻译:

香草酸作为磷脂酶 A2 和蛋白酶抑制剂:体外和计算分析

天然化合物的酶抑制可能代表了蛇咬伤血清治疗中的一种有价值的佐剂。这项工作的目的是评估香草酸和来自Bothrops spp 的酶之间可能的体外相互作用。和Crotalus durissus terrificus毒液,并且还提出了一种基于分子对接的理论,即它们如何相互作用。香草酸抑制由感应的磷脂酶活性矛头天牛(〜25%抑制); Bothrops atrox (~30%)、Bothrops jararacussu (~44%) 和C. d.诱导的酪蛋白分解活性了不起(~33%); B. jararacussu , B. atrox诱导的纤维蛋白原溶解, 和C. d. 了不起(100%); 由Bothrops moojeni (~45%) 和Bothrops jararaca (~66%)诱导的丝氨酸蛋白酶活性;B. moojeni (~26%)诱导的溶血活性;由B. atrox (~30%) 和B. jararacussu (~20%)诱导的溶栓活性;以及由C. d.诱导的血栓形成活动了不起(~8%)。当与B. moojeniB. atroxB. jararaca一起孵育时,该化合物还能够将柠檬酸盐血浆中的凝血时间延迟60、35和 75 秒, 分别。考虑到人和蛇毒磷脂酶 A 2和蛋白酶(涉及慢性炎症疾病)之间的高度同源性,所获得的结果扩展了香草酸未来制药用途的可能性。此外,这种化合物可用作佐剂,以改善目前对蛇毒受害者可用的治疗方法。
更新日期:2020-05-18
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