Synthesis, characterization and utilization of a new series of 1,2,3-triazole derivatives to neutralize some toxic activities of Bothrops jararaca snake venom

Nayanna de Melo Amorim; Luiz Carlos Simas Pereira Junior; Eladio Flores Sanchez; Gabriel Alves de Aquino; Vitor Ferreira; Sabrina Baptista Ferreira; André Lopes Fuly; Eduardo Coriolano de Oliveira

doi:10.1590/s2175-9790202X000X2e201143

Authors

Nayanna de Melo Amorim Department of Molecular and Cellular Biology, Institute of Biology, Federal Fluminense University, Niterói, RJ, Brazil
Luiz Carlos Simas Pereira Junior Department of Molecular and Cellular Biology, Institute of Biology, Federal Fluminense University, Niterói, RJ, Brazil
Eladio Flores Sanchez Research and Development Center, Ezequiel Dias Foundation, Belo Horizonte, MG, Brazil
Gabriel Alves de Aquino Department of Organic Chemistry, Institute of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
Vitor Ferreira Department of Pharmaceutical Technology, Faculty of Pharmacy, Federal Fluminense University, Niterói, RJ, Brazsil
Sabrina Baptista Ferreira Department of Organic Chemistry, Institute of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
André Lopes Fuly Department of Molecular and Cellular Biology, Institute of Biology, Federal Fluminense University, Niterói, RJ, Brazil https://orcid.org/0000-0002-5265-5258
Eduardo Coriolano de Oliveira Department of Molecular and Cellular Biology, Institute of Biology, Federal Fluminense University, Niterói, RJ, Brazil

DOI:

https://doi.org/10.1590/s2175-9790202X000X2e201143

Keywords:

1,2,3-triazole derivatives, Organic synthesis, Bothrops jararaca, Snake venom, Neutralization, Antivenom

Abstract

Snake envenomation is a public health problem, and while serum therapy prevents death, the local effects of venoms can lead to amputations or morbidities. Thus, alternative treatments deserve attention. In this study, we tested eight derivatives of 1,2,3-triazole against some toxic activities of Bothrops jararaca venom. The derivatives were synthesized, and their structures analyzed by infrared and nuclear magnetic resonance. After that, the ability of compounds to inhibit hemolysis, coagulation, proteolysis, hemorrhaging, edema, and lethal activities of B. jararaca venom was investigated. The derivatives were incubated with B. jararaca venom (incubation protocol), administered before (prevention protocol) or after (treatment protocol) injecting venom into the mice. Then, hemorrhaging assay occurred. As a result, most of the derivatives inhibited the activities, even if they were incubated, injected before or after B. jararaca venom. However, the derivatives TRI 07 and TRI 18 seemed to be the most efficient in impairing hemorrhaging. The derivatives showed a low drug score of toxicity based on an in silico technique. Therefore, the derivatives fulfilled physicochemical and biological requirements to become drugs, and they may be a brand new initiative for designing antivenom molecules to complement antivenom therapy to efficiently block tissue necrosis or any other local effects.

Downloads

Download data is not yet available.

References

Ascoët S, Ward M. Diagnostic and therapeutic value of aptamers in envenomation cases. Int J Mol Sci. 2020;21(10):3565-3591.

Boechat N, Ferreira ML, Bastos MM, Wardell JL, Wardell SM, Tiekink ER. [1-(3-Chlorophenyl)-1H-1,2,3-triazol-4-yl] methanol hemihydrate. Acta Crystallogr Sect E Struct Rep. 2011;67(Pt 11):2934-2935.

Campos LB, Pucca MB, Silva LC, Pessenda G, Filardi BA, Cerni FA, et al. Identification of cross-reactive human single-chain variable fragments against phospholipases A2 from Lachesis muta and Bothrops spp venoms. Toxicon. 2020;184:116-121.

Chippaux JP. Incidence and mortality due to snakebite in the Americas. PLoS Negl Trop Dis. 2017;11(6):e0005662.

Clark RF, McKinney PE, Chase PB, Walter FG. Immediate and delayed allergic reactions to Crotalidae Polyvalent Immune Fab (ovine) antivenom. Ann Emerg Med. 2002;39(6):671-677.

da Silva ACR, Pires AMG, Ramos CJB, Sanchez EF, Cavalcanti DN, Teixeira VL, et al. The seaweed Prasiola crispa (Chlorophyta) neutralizes toxic effects of Bothrops jararacussu snake venom. J Appl Phycol. 2017;29(2):781-788.

da Silva SL, Calgarotto AK, Chaar JS, Marangoni S. Isolation and characterization of ellagic acid derivatives isolated from Casearia sylvestris SW aqueous extract with anti-PLA2 activity. Toxicon . 2008;52(6):655-666.

Dart RC, Mcnally J. Efficacy, safety, and use of snake antivenoms in the United States. Ann Emerg Med . 2011;37(2):181-188.

de Farias IB, Morais-Zani K, Serino-Silva C, Sant’Anna SS, Da Rocha MMT, Grego KF, et al. Functional and proteomic comparison of Bothrops jararaca venom from captive specimens and the Brazilian Bothropic Reference Venom. J Proteomics. 2018;174:36-46.

de Oliveira EC, Cruz RAS, Amorim NM, Santos MG, Pereira-Junior LCS, Sanchez EF, et al. Protective effect of the plant extracts of Erythroxylum sp. against toxic effects induced by the venom of Lachesis muta snake. Molecules. 2016;21(10):1350-1364.

de Oliveira EC, Fernandes CP, Sanchez EF, Rocha LM, Fuly AL. Inhibitory effect of plant Manilkara subsericea against biological activities of Lachesis muta snake venom. Biomed Res Int. 2014;2014:408068.

Domingos TFS, Moura LA, Carvalho C, Campos VR, Jordão AK, Cunha AC, et al. Antivenom Effects of 1,2,3-Triazoles against Bothrops jararaca and Lachesis muta Snakes. Biomed Res Int . 2013;2013:294289-294296.

Faioli CN, Domingos TF, de Oliveira EC, Sanchez EF, Ribeiro S, Muricy G, et al. Appraisal of antiophidic potential of marine sponges against Bothrops jararaca and Lachesis muta venom. Toxins. 2013;5(10):1799-1813.

Frare BT, Resende YKS, Dornelas BC, Jorge MT, Ricarte VAS, Alves LM, et al. Clinical, laboratory, and therapeutic aspects of Crotalus durissus (South American Rattlesnake) Victims: A literature review. Biomed Res Int . 2019;2019:1345923.

Fuly AL, Machado OL, Alves EW, Carlini CR. Mechanism of inhibitory action on platelet activation of a phospholipase A2 isolated from Lachesis muta (Bushmaster) snake venom. Thromb Haemost. 1997;78(5):1372-1380.

Garcia ES, Guimarães JA, Prado JL. Purification and characterization of a sulfhydryl-dependent protease from Rhodnius prolixus midgut. Arch Biochem Biophys. 1978;188(2):315-322.

Gómez-Betancur I, Gogineni V, Salazar-Ospina A, León F. Perspective on the therapeutics of anti-snake venom. Molecules . 2019;24(3276):1-29.

Kharb R, Sharma PC, Yar MS. Pharmacological significance of triazole scaffold. J Enz Inhib Med Chem. 2011;26(1):1-21.

Knudsen C, Ledsgaard L, Dehli RI, Ahmadi S, Sørensen CV, Laustsen AH. Engineering and 263 design considerations for next-generation snakebite antivenoms. Toxicon . 2019;167:67-75.

Kondo H, Kondo S, Ikezawa H, Murata R, Ohsaka A. Studies on the quantitative method for the determination of hemorrhagic activity of Habu snake venom. Jpn J Med Sci Biol. 1960;13:43-51.

Kumar SS, Kavitha HP. Synthesis and biological applications of triazole derivatives - A review. Mini-Rev Org Chem. 2013;10(1):40-65.

Malik MS, Ahmed AS, Althagafi II, Ansari MA, Kamal A. Application of triazoles as bioisosteres and linkers in the development of microtubule targeting agents. RSC Med Chem. 2020;11(3):327-348.

Moura LA, de Almeida AC, da Silva AV, de Souza VR, Ferreira VF, Menezes MV, et al. Synthesis, anticlotting and antiplatelet effects of 1,2,3-triazoles derivatives. Med Chem. 2016;12(8):733-741.

Preciado LM, Comer J, Núñez V, Rey-Súarez P, Pereañez, JA. Inhibition of a snake venom metalloproteinase by the Flavonoid Myricetin. Molecules . 2018;23(10):2662.

Pucca MB, Cerni FA, Janke R, Bermúdez-Méndez E, Ledsgaard L, Barbosa JE, et al. History of envenoming therapy and current perspectives. Front Immunol. 2019;10:1598-1610.

Ren M, Malecela MN, Coke E, Abela-Ridder B. WHO’s Snakebite Envenoming Strategy for prevention and control. Lancet Glob Health. 2019;7(7):e837-e838.

Senise LV, Yamashita KM, Santoro ML. Bothrops jararaca envenomation: Pathogenesis of hemostatic disturbances and intravascular hemolysis. Exp Biol Med (Maywood). 2015;240(11):1528-1536.

Souza JF, de Oliveira EC, da Silva ACR, Silva VP, Kaplan MAC, Figueiredo MR, et al. Potential use of extract of the plant Schwartzia brasiliensis (Choisy) Bedell ex Gir.-Cañas against the toxic effects of the venom of Bothrops jararaca or B. jararacussu Biomed Pharmacother. 2020;125:109951-109958.

Strauch MA, Tomaz MA, Monteiro-Machado M, Cons BL, Patrão-Neto FC, Teixeira-Cruz JM, et al. Lapachol and synthetic derivatives: in vitro and in vivo activities against Bothrops snake venoms. PLoS ONE. 2019;14(1):e0211229.

Tasoulis T, Isbister GK. A review and database of snake venom proteomes. Toxins . 2017;9(9):290-313.

Villar JAFP, Lima FTD, Veber CL, Oliveira ARM, Calgarotto AK, Marangoni S, et al. Synthesis and evaluation of nitrostyrene derivative compounds, new snake venom phospholipase A2 inhibitors. Toxicon . 2008;51(8):1467-1478.

Williams DJ, Faiz MA, Abela-Ridder B, Ainsworth S, Bulfone TC, Nickerson AD, et al. Strategy for a globally coordinated response to a priority neglected tropical disease: Snakebite envenoming. PLoS Negl Trop Dis . 2019a;13(2):e0007059.

Williams HF, Layfield HJ, Vallance T, Patel K, Bicknell AB, Trim SA, et al. The urgent need to develop novel strategies for the diagnosis and treatment of snakebites. Toxins . 2019b;11(363):1-29.

Yamakawa M, Nozani M, Hokama Z. Fractionation of Sakishima-habu (Trimeresurus elegans) venom and lethal, hemorrhagic and edema-forming activities of the fractions. In: Ohsaka A, Hayashi K, Sawai Y (Eds.). Animal, plant and microbial toxins. New York: Plenum Press. 1976;97-109.

Zhou CH, Wang Y. Recent researches in triazole compounds as medicinal drugs. Curr Med Chem . 2012;19(2):239-280.

Synthesis, characterization and utilization of a new series of 1,2,3-triazole derivatives to neutralize some toxic activities of Bothrops jararaca snake venom

Authors

DOI:

Keywords:

Abstract

Downloads

References

Downloads

Published

Issue

Section

License

How to Cite

Funding data