Neutralising effects of small molecule toxin inhibitors on nanofractionated coagulopathic Crotalinae

来源 :药学学报(英文版) | 被引量 : 0次 | 上传用户:zhougtz
下载到本地 , 更方便阅读
声明 : 本文档内容版权归属内容提供方 , 如果您对本文有版权争议 , 可与客服联系进行内容授权或下架
论文部分内容阅读
Repurposing small molecule drugs and drug candidates is considered as a promising approach to revolutionise the treatment of snakebite envenoming.In this study,we investigated the inhibiting effects of the small molecules varespladib (nonspecific phospholipase A2 inhibitor),marimastat (broad spectrum matrix metalloprotease inhibitor) and dimercaprol (metal ion chelator) against coagulopathic toxins found in Crotalinae (pit vipers) snake venoms.Venoms from Bothrops asper,Bothropsjararaca,Calloselasma rhodostoma and Deinagkistrodon acutus were separated by liquid chromatography,followed by nanofractionation and mass spectrometry identification undertaken in parallel.Nanofractions of the venom toxins were then subjected to a high-throughput coagulation assay in the presence of different concentrations of the small molecules under study.Anticoagulant venom toxins were mostly identified as phospholipases A2,while procoagulant venom activities were mainly associated with snake venom metalloproteinases and snake venom serine proteases.Varespladib was found to effectively inhibit most anticoagulant venom effects,and also showed some inhibition against procoagulant toxins.Contrastingly,marimastat and dimercaprol were both effective inhibitors of procoagulant venom activities but showed little inhibitory capability against anticoagulant toxins.The information obtained from this study aids our understanding of the mechanisms of action of toxin inhibitor drug candidates,and highlights their potential as future snakebite treatments.
其他文献
会议
会议
Polyethylene glycols (PEGs) in general use are polydisperse molecules with molecular weight (MW) distributed around an average value applied in their designatio
会议
会议
会议
生命意识教育既是人的全面发展的内在要求,也是促进人的全面发展的重要手段.当前人类面临着严重的生存危机,其根本原因在于人们缺乏生命意识.作为义务教育阶段的生物学教学,
会议
会议
Pulmonary drug delivery has attracted increasing attention in biomedicine,and porous par-ticles can effectively enhance the aerosolization performance and bioav