Pub Date : 2024-01-12DOI: 10.2174/0126661217272344231208060944
Luiz Carlos Simas Pereira Junior, Nayanna de Melo Amorim, Eduardo Coriolano de Oliveira, Eladio Flores Sanchez, Vitor Francisco Ferreira, Gabriel Alves Souto de Aquino, Sabrina Baptista Ferreira, André Lopes Fuly
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. 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. 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. 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. 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. Thus, these new series of triazoles may help the development of molecules able to improve the treatment of L. muta envenoming. none
蛇咬伤是世界性的健康问题,会产生出血、组织坏死、血液凝固障碍、水肿和死亡等病理症状。虽然血清疗法能保护受害者免于死亡,但并不能防止患肢截肢。对十二种新系列的异构三唑类化合物 TRI 02、TRI 03、TRI 04、TRI 05、TRI 07、TRI 08、TRI 09、TRI 11、TRI 14、TRI 16、TRI 17 或 TRI 18 进行试验,以检测其对 L. muta 毒液的出血、致水肿、溶血、凝血或蛋白水解活性的影响。将这些衍生物与 L. muta 毒液进行孵育(孵育方案),然后进行毒性活性测试。此外,在使用这些衍生物之前(治疗方案)或之后(预防方案)注射鲎毒。大多数衍生物都能抑制鲎毒的蛋白水解或溶血活性,但只有 TRI 17 能抑制鲎毒的凝血活性。衍生物 TRI 03、TRI 05、TRI 07、TRI 14 或 TRI 17 可抑制出血;而 TRI 07、TRI 08 或 TRI 16 可抑制水肿。TRI 03、TRI 07 或 TRI 11 衍生物可抑制出血,即使它们是在 L. muta 毒液之后或之前给药也是如此。根据硅学研究,TRI 03、TRI 04、TRI 07、TRI 08、TRI 09、TRI 16、TRI 17 或 TRI 18 衍生物没有毒性。因此,这些新系列的三唑类化合物可能有助于开发出能更好地治疗鼠螨螫伤的分子。
{"title":"Novel 1,2,3-triazoles as Inhibitors of the Toxic Effects of the Venom of the Snake Lachesis muta muta","authors":"Luiz Carlos Simas Pereira Junior, Nayanna de Melo Amorim, Eduardo Coriolano de Oliveira, Eladio Flores Sanchez, Vitor Francisco Ferreira, Gabriel Alves Souto de Aquino, Sabrina Baptista Ferreira, André Lopes Fuly","doi":"10.2174/0126661217272344231208060944","DOIUrl":"https://doi.org/10.2174/0126661217272344231208060944","url":null,"abstract":"\u0000\u0000Snakebites 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.\u0000\u0000\u0000\u0000To 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.\u0000\u0000\u0000\u0000To 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.\u0000\u0000\u0000\u0000The 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.\u0000\u0000\u0000\u0000Most 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.\u0000\u0000\u0000\u0000Thus, these new series of triazoles may help the development of molecules able to improve the treatment of L. muta envenoming.\u0000\u0000\u0000\u0000none\u0000","PeriodicalId":438678,"journal":{"name":"Venoms and Toxins","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139532367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-29DOI: 10.2174/0126661217183829231108105708
F. Kazemi-Lomedasht, D. Shahbazzadeh, M. Behdani
Venom allergens have been identified in the venom of scorpion, snake, bee, wasp, etc. Some allergy reactions in humans may refer to the venom allergens. Phylogenetic analysis of venom allergens from the transcriptome of Hemiscorpius lepturus scorpion was the main aim of the study. Seven venom allergens: HLAllergen1, HLAllergen2, HLAllergen3, HLAllergen4, HLAllergen5, HLAllergen6, and HLAllergen7 have been identified in the venom of Hemiscorpius lepturus scorpion using venom gland transcriptome analysis. Primary, secondary and tertiary structures of the identified venom allergens were predicted using ExPASy ProtParam, PSIPRED, and SWISS MODEL servers. Phylogenetic tree was constructed using MEGA 11 software through neighbor-joining method with 1000 bootstraps. Structure analysis of identified venom allergens showed a molecular weight of between 46 to 52 kDa. Tertiary structure results showed that all predicted 3-D structures were in a normal range. Phylogenetic tree analysis showed that HLAllergen 3, 4 and 5 were formed single clades and HLAllergen 1, 2, 7, and 6 other clades However, further studies using proteomic analysis of H. lepturus are needed to confirm and compare with transcriptome data. Phylogenetic tree analysis showed that HLAllergen 3, 4 and 5 were formed single clade and HLAllergen 1, 2, 7, and 6 other clades.
{"title":"Identification and Phylogenetic Analysis of Venom Allergens from Transcriptome of Hemiscorpius lepturus Scorpion","authors":"F. Kazemi-Lomedasht, D. Shahbazzadeh, M. Behdani","doi":"10.2174/0126661217183829231108105708","DOIUrl":"https://doi.org/10.2174/0126661217183829231108105708","url":null,"abstract":"Venom allergens have been identified in the venom of scorpion, snake, bee, wasp, etc. Some allergy reactions in humans may refer to the venom allergens. Phylogenetic analysis of venom allergens from the transcriptome of Hemiscorpius lepturus scorpion was the main aim of the study. Seven venom allergens: HLAllergen1, HLAllergen2, HLAllergen3, HLAllergen4, HLAllergen5, HLAllergen6, and HLAllergen7 have been identified in the venom of Hemiscorpius lepturus scorpion using venom gland transcriptome analysis. Primary, secondary and tertiary structures of the identified venom allergens were predicted using ExPASy ProtParam, PSIPRED, and SWISS MODEL servers. Phylogenetic tree was constructed using MEGA 11 software through neighbor-joining method with 1000 bootstraps. Structure analysis of identified venom allergens showed a molecular weight of between 46 to 52 kDa. Tertiary structure results showed that all predicted 3-D structures were in a normal range. Phylogenetic tree analysis showed that HLAllergen 3, 4 and 5 were formed single clades and HLAllergen 1, 2, 7, and 6 other clades However, further studies using proteomic analysis of H. lepturus are needed to confirm and compare with transcriptome data. Phylogenetic tree analysis showed that HLAllergen 3, 4 and 5 were formed single clade and HLAllergen 1, 2, 7, and 6 other clades.","PeriodicalId":438678,"journal":{"name":"Venoms and Toxins","volume":"72 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139213714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-03DOI: 10.2174/0126661217243087231023093542
Rui Yan, Shan Zhang
Background: G. elegans is a highly useful medicinal plant with broad and superior clinical pharmacological effects. However, it also exhibits high toxicity to humans, so it must be used with extreme caution in clinical practice. Previous studies on G. elegans have mainly focused on its main ingredients from perspectives of pharmaceutical analysis, pharmacokinetics, and pharmacodynamics. The kinetic behavior of G. elegans' main metabolites in vivo has not yet been reported, which is also crucial for studying the herb's toxification and detoxification process. Aims: This study aimed to establish a quantitative method to describe the metabolic profile of the two main metabolites of koumine after oral administration of G. elegans to rats. Objective: The objective of this study was to test two major metabolites of G. elegans in rat urine after administration using a rapid and sensitive high-performance liquid chromatographic-tandem mass spectrometric (HPLC-MS/MS) method developed in advance. Methods: A Kromasil C18 column was used as the stationary phase for chromatographic separation, with an isocratic mobile phase consisting of mixture of water (2 mM ammonium formate), formic acid, and methanol (25:0.05:75, v/v/v) at a flow rate of 0.40 mL/min. The mass spectrometer was equipped with an electrospray ionization (ESI) source operating in positive ionization mode, and detection was performed using a selective reaction monitoring (SRM) mode. Detection was performed in selective reaction monitoring (SRM) mode. Protein precipitation was used to pretreat the rat urine samples before analysis, with acetonitrile as the precipitation solvent. In this study, a "relative quantification" strategy was employed, which avoided the expensive and time-consuming separation of standard substances. The assay was validated in terms of specificity, linearity, precision, stability, recovery, and other aspects. Results: The intra- and inter-day precision values were less than 12.7%. The recoveries at three different concentrations were all above 73.1%. The stability study showed that the analytes were stable during the experiment. The method was then used to study the kinetic profiles of N-demethylkoumine and N-oxidatekoumine in rat urine for the first time. Conclusion: In this study, the established LC/MS method was fully validated and proven to be sensitive and accurate for the simultaneous determination of the two main metabolites of G. elegans in rats' urine samples. These results could provide references for the safe use of koumine and G. elegans in clinical applications.
{"title":"Simultaneous Determination of Two Metabolites of Gelsemium elegans by LC-MS/MS in Rat Urine and its Application to Pharmacokinetic Study","authors":"Rui Yan, Shan Zhang","doi":"10.2174/0126661217243087231023093542","DOIUrl":"https://doi.org/10.2174/0126661217243087231023093542","url":null,"abstract":"Background: G. elegans is a highly useful medicinal plant with broad and superior clinical pharmacological effects. However, it also exhibits high toxicity to humans, so it must be used with extreme caution in clinical practice. Previous studies on G. elegans have mainly focused on its main ingredients from perspectives of pharmaceutical analysis, pharmacokinetics, and pharmacodynamics. The kinetic behavior of G. elegans' main metabolites in vivo has not yet been reported, which is also crucial for studying the herb's toxification and detoxification process. Aims: This study aimed to establish a quantitative method to describe the metabolic profile of the two main metabolites of koumine after oral administration of G. elegans to rats. Objective: The objective of this study was to test two major metabolites of G. elegans in rat urine after administration using a rapid and sensitive high-performance liquid chromatographic-tandem mass spectrometric (HPLC-MS/MS) method developed in advance. Methods: A Kromasil C18 column was used as the stationary phase for chromatographic separation, with an isocratic mobile phase consisting of mixture of water (2 mM ammonium formate), formic acid, and methanol (25:0.05:75, v/v/v) at a flow rate of 0.40 mL/min. The mass spectrometer was equipped with an electrospray ionization (ESI) source operating in positive ionization mode, and detection was performed using a selective reaction monitoring (SRM) mode. Detection was performed in selective reaction monitoring (SRM) mode. Protein precipitation was used to pretreat the rat urine samples before analysis, with acetonitrile as the precipitation solvent. In this study, a \"relative quantification\" strategy was employed, which avoided the expensive and time-consuming separation of standard substances. The assay was validated in terms of specificity, linearity, precision, stability, recovery, and other aspects. Results: The intra- and inter-day precision values were less than 12.7%. The recoveries at three different concentrations were all above 73.1%. The stability study showed that the analytes were stable during the experiment. The method was then used to study the kinetic profiles of N-demethylkoumine and N-oxidatekoumine in rat urine for the first time. Conclusion: In this study, the established LC/MS method was fully validated and proven to be sensitive and accurate for the simultaneous determination of the two main metabolites of G. elegans in rats' urine samples. These results could provide references for the safe use of koumine and G. elegans in clinical applications.","PeriodicalId":438678,"journal":{"name":"Venoms and Toxins","volume":"31 9‐10","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135873025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}