Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Journal of Current Toxicology and Venomics
  4. Volume 4, Issue 1
  5. Article
Volume 4, Issue 1
  • ISSN: 2950-5704
  • E-ISSN: 2950-5712

Abstract

Background

Snakebites are a worldwide health problem and produce pathological symptoms, such as hemorrhage, tissue necrosis, blood coagulation disorder, edema, and death. Although serum therapy protects victims from death, it does not prevent amputation of the affected limb. Therefore, alternative treatments deserve attention.

Objective

To test a new series of twelve disubstituted triazoles, TRI 02, TRI 03, TRI 04, TRI 05, TRI 07, TRI 08, TRI 09, TRI 11, TRI 14, TRI 16, TRI 17, and TRI 18 against the hemorrhagic, edematogenic, hemolytic, coagulant, and proteolytic activities of venom.

Methods

The derivatives were incubated with venom (incubation protocol), then the toxic activities were measured. venom was injected before (treatment protocol) or after (prevention protocol) the derivatives.

Results

Most of the derivatives inhibited the proteolytic and hemolytic activity of venom, but only TRI 17 inhibited coagulation activity. The derivatives TRI 03, TRI 05, TRI 07, TRI 14, and TRI 17 inhibited hemorrhage, while TRI 07, TRI 08, and TRI 16 inhibited edema. The derivatives TRI 03, TRI 07, and TRI 11 inhibited hemorrhage whether they were administered before or after venom. According to tool, TRI 03, TRI 04, TRI 07, TRI 08, TRI 09, TRI 16, TRI 17, and TRI 18 were not toxic. The derivatives did not violate Lipinksi’s rule of five.

Conclusion

These triazoles serve as molecules able to improve the treatment of envenoming.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/jctv/10.2174/0126661217272344231208060944
2024-01-01
2024-11-26

  • From This Site

    /content/journals/jctv/10.2174/0126661217272344231208060944
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. GutiérrezJ.M. CalveteJ.J. HabibA.G. HarrisonR.A. WilliamsD.J. WarrellD.A. Snakebite envenoming.Nat. Rev. Dis. Primers2017317063121
     [Google Scholar]
  2. ChippauxJ.P. Snakebite envenomation turns again into a neglected tropical disease!J. Venom. Anim. Toxins Incl. Trop. Dis.20172313810.1186/s40409‑017‑0127‑6 28804495
     [Google Scholar]
  3. WHOSnakebite envenoming.2021Available from: https://www.who.int/news-room/fact-sheets/detail/snakebite-envenoming (Accessed on February 2021).
  4. WilliamsD.J. FaizM.A. Abela-RidderB. Strategy for a globally coordinated response to a priority neglected tropical disease: Snakebite envenoming.PLoS Negl. Trop. Dis.2019132e000705910.1371/journal.pntd.0007059 30789906
     [Google Scholar]
  5. da SilvaA.R. AnholetiM.C. PietroluongoM. Utilization of the plant Clusia fluminensis planch & triana against some toxic activities of the venom of Bothrops jararaca and B. jararacussu snake venom toxic activities.Curr. Top. Med. Chem.201919221990200210.2174/1568026619666190724160711 31339072
     [Google Scholar]
  6. Mora-ObandoD. PlaD. LomonteB. Guerrero-VargasJ.A. AyerbeS. CalveteJ.J. Antivenomics and in vivo preclinical efficacy of six Latin American antivenoms towards south-western Colombian Bothrops asper lineage venoms.PLoS Negl. Trop. Dis.2021152e000907310.1371/journal.pntd.0009073 33524033
     [Google Scholar]
  7. CañasC.A. Castaño-ValenciaS. Castro-HerreraF. The Colombian bushmasters Lachesis acrochorda (García, 1896) and Lachesis muta (Linnaeus, 1766): Snake species, venoms, envenomation, and its management.Toxicon202323023010715210.1016/j.toxicon.2023.107152 37178796
     [Google Scholar]
  8. Ministério da Saúde2023Available form: http://tabnet.datasus.gov.br/cgi/deftohtm.exe?sinannet/cnv/animaisbr.def (Cited 25/05/2023).
  9. WarrellD.A. Snakebites in Central and South America: Epidemiology, clinical features, and clinical management.The venomous reptiles of the western hemisphere.IthacaCornell University Press2004709761
     [Google Scholar]
  10. Barrio-AmorósC.L. CorralesG. RodríguezS. CulebrasJ. DwyerQ. FloresD.A. The Bushmasters (Lachesis spp.): Queens of the rainforest.Reptiles Amphib.202027335838110.17161/randa.v27i3.14978
     [Google Scholar]
  11. MadrigalM. SanzL. Flores-DíazM. Snake venomics across genus Lachesis. Ontogenetic changes in the venom composition of Lachesis stenophrys and comparative proteomics of the venoms of adult Lachesis melanocephala and Lachesis acrochorda.J. Proteomics2012777728029710.1016/j.jprot.2012.09.003 22982523
     [Google Scholar]
  12. IUCNThe IUCN Red List of threatened species.2023Available from: https://www.iucnredlist.org (Accessed on February 2023).
  13. ZamudioK. GreeneH.W. Phylogeography of the bushmaster (Lachesis muta: Viperidae): implications for neotropical biogeography, systematics, and conservation.Biol. J. Linn. Soc. Lond.199762342144210.1006/bijl.1997.0162
     [Google Scholar]
  14. Angel-CamiloK.L. Guerrero-VargasJ.A. CarvalhoE.F. Disorders on cardiovascular parameters in rats and in human blood cells caused by Lachesis acrochorda snake venom.Toxicon2020184918019110.1016/j.toxicon.2020.06.009 32585218
     [Google Scholar]
  15. StephanoM.A. GuidolinR. HigashiH.G. TambourgiD.V. Sant’AnnaO.A. The improvement of the therapeutic anti-Lachesis muta serum production in horses.Toxicon200545446747310.1016/j.toxicon.2004.12.006 15733568
     [Google Scholar]
  16. SanzL. EscolanoJ. FerrettiM. Snake venomics of the south and central american bushmasters. Comparison of the toxin composition of Lachesis muta gathered from proteomic versus transcriptomic analysis.J. Proteomics2008711466010.1016/j.jprot.2007.10.004 18541473
     [Google Scholar]
  17. Diniz-SousaR. MoraesJ.N. Rodrigues-da-SilvaT.M. OliveiraC.S. CaldeiraC.A.S. A brief review on the natural history, venomics and the medical importance of bushmaster (Lachesis) pit viper snakes.Toxicon X202071010005310.1016/j.toxcx.2020.100053 32793880
     [Google Scholar]
  18. de LimaM.E. Fortes-DiasC.L. CarliniC.R. GuimarãesJ.A. Toxinology in Brazil: A big challenge for a rich biodiversity.Toxicon20105671084109110.1016/j.toxicon.2010.05.005 20685368
     [Google Scholar]
  19. CameyK.U. VelardeD.T. SanchezE.F. Pharmacological characterization and neutralization of the venoms used in the production of Bothropic antivenom in Brazil.Toxicon200240550150910.1016/S0041‑0101(01)00245‑8 11821121
     [Google Scholar]
  20. PatikornC. IsmailA.K. Zainal AbidinS.A. OthmanI. ChaiyakunaprukN. TaychakhoonavudhS. Potential economic and clinical implications of improving access to snake antivenom in five ASEAN countries: A cost-effectiveness analysis.PLoS Negl. Trop. Dis.20221611e001091510.1371/journal.pntd.0010915 36383562
     [Google Scholar]
  21. SaethangT. SomparnP. PayungpornS. Identification of Daboia siamensis venome using integrated multi-omics data.Sci. Rep.20221211314010.1038/s41598‑022‑17300‑1 35907887
     [Google Scholar]
  22. GutiérrezJ.M. Improving antivenom availability and accessibility: Science, technology, and beyond.Toxicon201260467668710.1016/j.toxicon.2012.02.008 22781134
     [Google Scholar]
  23. LeeL.P. TanC.H. KhomvilaiS. SitprijaV. ChaiyabutrN. TanK.Y. Characterizing and applying immunoglobulins in snakebite diagnostics: A simple and rapid venom detection assay for four medically important snake species in Southeast Asia.Int. J. Biol. Macromol.2023236112372712375410.1016/j.ijbiomac.2023.123727 36863668
     [Google Scholar]
  24. Simas PereiraJunior LC Coriolano de OliveiraE. Valle RorigT.D. The plant Stryphnodendron adstringens (Mart.) Coville as a neutralizing source against some toxic activities of Bothrops jararacussu snake venom.Toxicon202018618618219010.1016/j.toxicon.2020.08.011 32822735
     [Google Scholar]
  25. MorsW.B. NascimentoM.C. PereiraB.M. PereiraN.A. Plant natural products active against snake bite--the molecular approach.Phytochemistry200055662764210.1016/S0031‑9422(00)00229‑6 11130675
     [Google Scholar]
  26. SinghA. SinghK. SharmaA. 1,2,3‐Triazole Derivatives as an Emerging Scaffold for Antifungal Drug Development against Candida albicans: A Comprehensive Review.Chem. Biodivers.2023205e20230002410.1002/cbdv.202300024 37017338
     [Google Scholar]
  27. DantasW.M. de OliveiraV.N.M. SantosD.A.L. Searching anti-zika virus activity in 1h-1,2,3-triazole based compounds.Molecules20212619586910.3390/molecules26195869 34641413
     [Google Scholar]
  28. ConstantinescuT. LunguC.N. Anticancer activity of natural and synthetic chalcones.Int. J. Mol. Sci.202122211130610.3390/ijms222111306 34768736
     [Google Scholar]
  29. MouraL.A. de AlmeidaA.C.M. da SilvaA.V. Synthesis, anticlotting and antiplatelet effects of 1,2,3-triazoles derivatives.Med. Chem.201612873374110.2174/1573406412666160502153417 27140186
     [Google Scholar]
  30. CamposV.R. AbreuP.A. CastroH.C. Synthesis, biological, and theoretical evaluations of new 1,2,3-triazoles against the hemolytic profile of the Lachesis muta snake venom.Bioorg. Med. Chem.200917217429743410.1016/j.bmc.2009.09.031 19815419
     [Google Scholar]
  31. SouzaJ.F. SantanaM.V.S. da SilvaA.C.R. Study on the synthesis and structure-activity relationship of 1,2,3-triazoles against toxic activities of Bothrops jararaca venom.Zeitschrift für Naturfors C202277(11-12)459471
     [Google Scholar]
  32. KharbR. SharmaP.C. YarM.S. Pharmacological significance of triazole scaffold.J. Enzyme Inhib. Med. Chem.201126112110.3109/14756360903524304 20583859
     [Google Scholar]
  33. GonnetL. BaronM. BaltasM. Synthesis of biologically relevant 1,2,3- and 1,3,4-triazoles: from classical pathway to green chemistry.Molecules20212618566710.3390/molecules26185667 34577138
     [Google Scholar]
  34. AmorimN.M. PereiraJunior LCS SanchezE.F. Synthesis, characterization and utilization of a new series of 1,2,3-triazole derivatives to neutralize some toxic activities of Bothrops jararaca snake venom.Braz. J. Pharm. Sci.202258e20114310.1590/s2175‑9790202x000x2e201143
     [Google Scholar]
  35. GarciaE.S. GuimarãesJ.A. PradoJ.L. Purification and characterization of a sulfhydryl-dependent protease from Rhodnius prolixus midgut.Arch. Biochem. Biophys.1978188231532210.1016/S0003‑9861(78)80015‑0 28087
     [Google Scholar]
  36. FulyA.L. MachadoO.L.T. AlvesE.W. CarlinisC.R. Mechanism of inhibitory action on platelet activation of a phospholipase A2 isolated from Lachesis muta (Bushmaster) snake venom.Thromb. Haemost.19977851372138010.1055/s‑0038‑1665414 9408022
     [Google Scholar]
  37. KondoH. KondoS. IkezawaH. MurataR. OhsakaA. Studies on the quantitative method for determination of hemorrhagic activity of Habu snake venom.Jpn. J. Med. Sci. Biol.1960131-2435110.7883/yoken1952.13.43 13853435
     [Google Scholar]
  38. Sannanaik VishwanathB. Manjunatha KiniR. Veerabasappa GowdaT. Characterization of three edema-inducing phospholipase A2 enzymes from habu (Trimeresurus flavoviridis) venom and their interaction with the alkaloid aristolochic acid.Toxicon198725550151510.1016/0041‑0101(87)90286‑8 3617087
     [Google Scholar]
  39. BoechatN. PinheiroL.C.S. Santos-FilhoO.A. SilvaI.C. Design and synthesis of new N-(5-trifluoromethyl)-1H-1,2,4-triazol-3-yl benzenesulfonamides as possible antimalarial prototypes.Molecules20111698083809710.3390/molecules16098083 21934646
     [Google Scholar]
  40. KonrathE.L. StrauchI. BoeffD.D. ArboM.D. The potential of Brazilian native plant species used in the therapy for snakebites: A literature review.Toxicon2022217217174010.1016/j.toxicon.2022.08.002 35952835
     [Google Scholar]
  41. Coriolano de OliveiraE. Alves Soares CruzR. de Mello AmorimN. Protective effect of the plant extracts of Erythroxylum sp. against toxic effects induced by the venom of Lachesis muta snake.Molecules20162110135010.3390/molecules21101350 27727185
     [Google Scholar]
  42. ChazinE. MartinsL. de SouzaM.V. Synthesis and biological evaluation of novel 1,3-benzoxathiol-2-one sulfonamides against toxic activities of the venom of Bothrops jararaca and Bothrops jararacussu snakes.J. Braz. Chem. Soc.202233121210.21577/0103‑5053.20210119
     [Google Scholar]
  43. GutiérrezJ.M. AlbulescuL.O. ClareR.H. The search for natural and synthetic inhibitors that would complement antivenoms as therapeutics for snakebite envenoming.Toxins202113745110.3390/toxins13070451 34209691
     [Google Scholar]
  44. KeriR.S. PatilS.A. BudagumpiS. NagarajaB.M. Triazole: A promising antitubercular agent.Chem. Biol. Drug Des.201586441042310.1111/cbdd.12527 25643871
     [Google Scholar]
  45. StrauchM.A. TomazM.A. Monteiro-MachadoM. Lapachol and synthetic derivatives: In vitro and in vivo activities against Bothrops snake venoms.PLoS One2019141e021122910.1371/journal.pone.0211229 30689661
     [Google Scholar]
  46. AlamM.I. QuasimiH. KumarA. Protective effects of novel diazepinone derivatives in snake venom induced sterile inflammation in experimental animals.Eur. J. Pharmacol.2022928517509510.1016/j.ejphar.2022.175095 35728626
     [Google Scholar]
  47. SalvadorG.H.M. BorgesR.J. LomonteB. LewinM.R. FontesM.R.M. The synthetic varespladib molecule is a multi-functional inhibitor for PLA2 and PLA2-like ophidic toxins.Biochim. Biophys. Acta, Gen. Subj.20211865712991310.1016/j.bbagen.2021.129913 33865953
     [Google Scholar]
  48. Henao CastañedaI.C. PereañezJ.A. PreciadoL.M. Synthetic inhibitors of snake venom enzymes: Thioesters derived from 2-sulfenyl ethylacetate.Pharmaceuticals20191228010.3390/ph12020080 31126073
     [Google Scholar]
  49. de la RosaG. PastorN. AlagónA. CorzoG. Synthetic peptide antigens derived from long-chain alpha-neurotoxins: Immunogenicity effect against elapid venoms.Peptides2017882808610.1016/j.peptides.2016.12.006 28010961
     [Google Scholar]
  50. CamperiS.A. AcostaG. BarredoG.R. Synthetic peptides to produce antivenoms against the Cys-rich toxins of arachnids.Toxicon X20206510003810.1016/j.toxcx.2020.100038 32550593
     [Google Scholar]
  51. GaoF. WangT. XiaoJ. HuangG. Antibacterial activity study of 1,2,4-triazole derivatives.Eur. J. Med. Chem.2019173127428110.1016/j.ejmech.2019.04.043 31009913
     [Google Scholar]
  52. AlamM.M. 1,2,3-Triazole hybrids as anticancer agents: A review.Arch. Pharm.20023551e2100158
     [Google Scholar]
  53. YangW. XuanB. LiX. SiH. ChenA. Therapeutic potential of 1,2,3‐triazole hybrids for leukemia treatment.Arch Pharm20223559220010610.1002/ardp.202200106 35532286
     [Google Scholar]
  54. OlaobaO.T. Karina dos SantosP. Selistre-de-AraujoH.S. Ferreira de SouzaD.H. Snake venom metalloproteinases (SVMPs): A structure-function update.Toxicon X20207710005210.1016/j.toxcx.2020.100052 32776002
     [Google Scholar]
  55. VaiyapuriS. WagstaffS.C. HarrisonR.A. GibbinsJ.M. HutchinsonE.G. Evolutionary analysis of novel serine proteases in the venom gland transcriptome of Bitis gabonica rhinoceros.PLoS One201166e2153210.1371/journal.pone.0021532 21731776
     [Google Scholar]
  56. XiaoH. PanH. LiaoK. YangM. HuangC. Snake venom PLA2, a promising target for broad-spectrum antivenom drug development.BioMed Res. Int.2017201711010.1155/2017/6592820 29318152
     [Google Scholar]
  57. DomingosT.F.S. MouraL.A. CarvalhoC. Antivenom effects of 1,2,3-triazoles against Bothrops jararaca and Lachesis muta snakes.BioMed Res. Int.201320131710.1155/2013/294289 23710441
     [Google Scholar]
/content/journals/jctv/10.2174/0126661217272344231208060944
Loading
Novel 1,2,3-triazoles as Inhibitors of the Toxic Effects of the Venom of the Snake Lachesis muta muta
J. Curr. Toxicol. Venomics 4, E120124225594 (2024); https://doi.org/10.2174/0126661217272344231208060944
/content/journals/jctv/10.2174/0126661217272344231208060944
/content/journals/jctv/10.2174/0126661217272344231208060944
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher's website along with the published article.

file format download Download

  • Article Type:     Research Article
Keyword(s): antivenom; lachesis muta muta; medicinal chemistry; neutralization; snake venom; Triazole
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test