In vitro and in vivo evaluation of 2-aminoalkanol and 1,2-alkanediamine derivatives against Strongyloides venezuelensis

Background: Strongyloidiasis is a parasitic disease widely present in tropical and subtropical areas. Strongyloides stercoralis represents the main species that infects human beings. Ivermectin is the current drug of choice; however, issues related with treatment failure in patients with diabetes or...

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Autores:
Legarda Ceballos, Ana Lucya
López Aban, Julio
Del Olmo, Esther
Escarcena, Ricardo
Bustos, Luis Antonio
Rojas Caraballo, José Vicente
Vicente, Belén
Fernández Soto, Pedro
San Feliciano, Arturo
Muro, Antonio
Tipo de recurso:
Article of journal
Fecha de publicación:
2016
Institución:
Universidad Cooperativa de Colombia
Repositorio:
Repositorio UCC
Idioma:
OAI Identifier:
oai:repository.ucc.edu.co:20.500.12494/1009
Acceso en línea:
https://hdl.handle.net/20.500.12494/1009
Palabra clave:
Strongyloidiasis
Alkanediamine
Anthelmintics
Rights
openAccess
License
Licencia CC
id COOPER2_43347dab7e97b7382a277af8653d05cf
oai_identifier_str oai:repository.ucc.edu.co:20.500.12494/1009
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network_name_str Repositorio UCC
repository_id_str
dc.title.spa.fl_str_mv In vitro and in vivo evaluation of 2-aminoalkanol and 1,2-alkanediamine derivatives against Strongyloides venezuelensis
title In vitro and in vivo evaluation of 2-aminoalkanol and 1,2-alkanediamine derivatives against Strongyloides venezuelensis
spellingShingle In vitro and in vivo evaluation of 2-aminoalkanol and 1,2-alkanediamine derivatives against Strongyloides venezuelensis
Strongyloidiasis
Alkanediamine
Anthelmintics
title_short In vitro and in vivo evaluation of 2-aminoalkanol and 1,2-alkanediamine derivatives against Strongyloides venezuelensis
title_full In vitro and in vivo evaluation of 2-aminoalkanol and 1,2-alkanediamine derivatives against Strongyloides venezuelensis
title_fullStr In vitro and in vivo evaluation of 2-aminoalkanol and 1,2-alkanediamine derivatives against Strongyloides venezuelensis
title_full_unstemmed In vitro and in vivo evaluation of 2-aminoalkanol and 1,2-alkanediamine derivatives against Strongyloides venezuelensis
title_sort In vitro and in vivo evaluation of 2-aminoalkanol and 1,2-alkanediamine derivatives against Strongyloides venezuelensis
dc.creator.fl_str_mv Legarda Ceballos, Ana Lucya
López Aban, Julio
Del Olmo, Esther
Escarcena, Ricardo
Bustos, Luis Antonio
Rojas Caraballo, José Vicente
Vicente, Belén
Fernández Soto, Pedro
San Feliciano, Arturo
Muro, Antonio
dc.contributor.author.none.fl_str_mv Legarda Ceballos, Ana Lucya
López Aban, Julio
Del Olmo, Esther
Escarcena, Ricardo
Bustos, Luis Antonio
Rojas Caraballo, José Vicente
Vicente, Belén
Fernández Soto, Pedro
San Feliciano, Arturo
Muro, Antonio
dc.subject.spa.fl_str_mv Strongyloidiasis
Alkanediamine
Anthelmintics
topic Strongyloidiasis
Alkanediamine
Anthelmintics
description Background: Strongyloidiasis is a parasitic disease widely present in tropical and subtropical areas. Strongyloides stercoralis represents the main species that infects human beings. Ivermectin is the current drug of choice; however, issues related with treatment failure in patients with diabetes or infected with T-lymphotropic virus-1 make the identification of new molecules for alternative treatment a priority. In the present study, the activity of sphingosine-related aminoalcohol and diamine were evaluated against Strongyloides venezuelensis third-stage larva (L3) cultures and experimental infections in mice. Methods: The efficacy of each compound against L3 was assessed using both XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) assay and microscopic observation with concentrations ranging from 1 to 350 μM. Cytotoxicity was evaluated using J774.2 macrophage cell line and XTT assay. Lethal concentration 50 (LC50), selectivity index (SI) and structure-activity relationships were established. The activity compounds 4 (2-(ethylamino) hexadecan-1-ol), 6 (2-(butylamino) hexadecan-1-ol), 17 (tert-butyl N-(1-aminododecan-2-yl) carbamate) and 18 (tert-butyl-N-(1-aminohexadecan-2-yl) carbamate) were further assessed against experimental S. venezuelensis infections in CD1 mice measuring reductions in the numbers of parthenogenetic females and egg passed in faeces. Mice were infected with 3,000 L3 and treated with 20 mg/kg/day for five days. Results: In the screening study of 15 aminoalcohols [lauryl (n = 9); palmityl (n = 13); stearyl (n = 15) and alcohol derivatives], the presence of a palmitol chain was associated with the highest efficacy against L3 (LC50 31.9–39. 1 μM). Alkylation of the 2-amino group with medium size fragments as ethyl or n-butyl showed the best larvicidal activity. The dialkylation did not improve efficacy. Aminoalcohols 4 and 6 showed the highest SI (1.5 and 1.6, respectively). With respect to diamine derivative compounds, a chain size of sixteen carbon atoms (palmitoyl chain, n = 13), and the alkylation of the 2-amino group with medium-sized fragments, were associated with the highest lethal activities. The presence of carbamoyl group in diamines 17 and 18 yielded high SI (1.7 and 1.4, respectively). Infected mice treated with aminoalcohol 6 showed reduction in parthenogenetic females (59 %) and eggs in faeces (51 %). Conclusions: These results support the potentiality of aminoalcohol and diamine sphingosine-related compounds as suitable prototypes for developing new promising drugs against strongyloidiasis.
publishDate 2016
dc.date.issued.none.fl_str_mv 2016-06-28
dc.date.accessioned.none.fl_str_mv 2017-08-10T20:28:43Z
dc.date.available.none.fl_str_mv 2017-08-10T20:28:43Z
dc.type.none.fl_str_mv Artículo
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dc.identifier.bibliographicCitation.spa.fl_str_mv Legarda Ceballo, A. L., López Aban, J., Del Olmo, E., Escarcena, R., Bustos, L. A., Rojas Caraballo, J., Vicente, B., Fernández Soto, P., San Feliciano, A., & Muro, A.. (2016). In vitro and in vivo evaluation of 2-aminoalkanol and 1,2-alkanediamine derivatives against Strongyloides venezuelensis. Parasites and Vectors , 9(9), 2-9
url https://hdl.handle.net/20.500.12494/1009
identifier_str_mv Legarda Ceballo, A. L., López Aban, J., Del Olmo, E., Escarcena, R., Bustos, L. A., Rojas Caraballo, J., Vicente, B., Fernández Soto, P., San Feliciano, A., & Muro, A.. (2016). In vitro and in vivo evaluation of 2-aminoalkanol and 1,2-alkanediamine derivatives against Strongyloides venezuelensis. Parasites and Vectors , 9(9), 2-9
dc.relation.isversionof.spa.fl_str_mv https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924291/
dc.rights.cc.none.fl_str_mv Licencia CC
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http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.publisher.spa.fl_str_mv Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Programa de Medicina, Santa Marta, Colombia, 00000
dc.publisher.program.spa.fl_str_mv Medicina
dc.publisher.place.spa.fl_str_mv Santa Marta
institution Universidad Cooperativa de Colombia
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spelling Legarda Ceballos, Ana LucyaLópez Aban, JulioDel Olmo, EstherEscarcena, RicardoBustos, Luis AntonioRojas Caraballo, José VicenteVicente, BelénFernández Soto, PedroSan Feliciano, ArturoMuro, Antonio2017-08-10T20:28:43Z2017-08-10T20:28:43Z2016-06-28https://hdl.handle.net/20.500.12494/1009Legarda Ceballo, A. L., López Aban, J., Del Olmo, E., Escarcena, R., Bustos, L. A., Rojas Caraballo, J., Vicente, B., Fernández Soto, P., San Feliciano, A., & Muro, A.. (2016). In vitro and in vivo evaluation of 2-aminoalkanol and 1,2-alkanediamine derivatives against Strongyloides venezuelensis. Parasites and Vectors , 9(9), 2-9Background: Strongyloidiasis is a parasitic disease widely present in tropical and subtropical areas. Strongyloides stercoralis represents the main species that infects human beings. Ivermectin is the current drug of choice; however, issues related with treatment failure in patients with diabetes or infected with T-lymphotropic virus-1 make the identification of new molecules for alternative treatment a priority. In the present study, the activity of sphingosine-related aminoalcohol and diamine were evaluated against Strongyloides venezuelensis third-stage larva (L3) cultures and experimental infections in mice. Methods: The efficacy of each compound against L3 was assessed using both XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) assay and microscopic observation with concentrations ranging from 1 to 350 μM. Cytotoxicity was evaluated using J774.2 macrophage cell line and XTT assay. Lethal concentration 50 (LC50), selectivity index (SI) and structure-activity relationships were established. The activity compounds 4 (2-(ethylamino) hexadecan-1-ol), 6 (2-(butylamino) hexadecan-1-ol), 17 (tert-butyl N-(1-aminododecan-2-yl) carbamate) and 18 (tert-butyl-N-(1-aminohexadecan-2-yl) carbamate) were further assessed against experimental S. venezuelensis infections in CD1 mice measuring reductions in the numbers of parthenogenetic females and egg passed in faeces. Mice were infected with 3,000 L3 and treated with 20 mg/kg/day for five days. Results: In the screening study of 15 aminoalcohols [lauryl (n = 9); palmityl (n = 13); stearyl (n = 15) and alcohol derivatives], the presence of a palmitol chain was associated with the highest efficacy against L3 (LC50 31.9–39. 1 μM). Alkylation of the 2-amino group with medium size fragments as ethyl or n-butyl showed the best larvicidal activity. The dialkylation did not improve efficacy. Aminoalcohols 4 and 6 showed the highest SI (1.5 and 1.6, respectively). With respect to diamine derivative compounds, a chain size of sixteen carbon atoms (palmitoyl chain, n = 13), and the alkylation of the 2-amino group with medium-sized fragments, were associated with the highest lethal activities. The presence of carbamoyl group in diamines 17 and 18 yielded high SI (1.7 and 1.4, respectively). Infected mice treated with aminoalcohol 6 showed reduction in parthenogenetic females (59 %) and eggs in faeces (51 %). Conclusions: These results support the potentiality of aminoalcohol and diamine sphingosine-related compounds as suitable prototypes for developing new promising drugs against strongyloidiasis.josev.rojas@campusucc.edu.coUniversidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Programa de Medicina, Santa Marta, Colombia, 00000MedicinaSanta Martahttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924291/StrongyloidiasisAlkanediamineAnthelminticsIn vitro and in vivo evaluation of 2-aminoalkanol and 1,2-alkanediamine derivatives against Strongyloides venezuelensisArtículohttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1http://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionLicencia CCinfo:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2PublicationORIGINAL3.pdf3.pdfapplication/pdf582366https://repository.ucc.edu.co/bitstreams/ade82826-5663-4821-9fa3-6005717c409b/download037d44e3a9d8f00e2e323fcc0e11e890MD51TEXT3.pdf.txt3.pdf.txtExtracted texttext/plain45131https://repository.ucc.edu.co/bitstreams/cdf625a5-0e2b-44ac-9ed7-6d5260b08777/downloade52aa24a07faf7603a06e23a8cfbedfdMD53THUMBNAIL3.pdf.jpg3.pdf.jpgIM Thumbnailimage/jpeg17495https://repository.ucc.edu.co/bitstreams/abde7a56-eb8b-4675-bd43-37e8c9805bda/download39eca8e3ece4f2f5298f1c854628584bMD54LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://repository.ucc.edu.co/bitstreams/66356b69-0f9b-4131-9c57-a96ee88affcd/download8a4605be74aa9ea9d79846c1fba20a33MD5220.500.12494/1009oai:repository.ucc.edu.co:20.500.12494/10092024-08-10 22:45:07.275open.accesshttps://repository.ucc.edu.coRepositorio Institucional Universidad Cooperativa de Colombiabdigital@metabiblioteca.comTk9URTogUExBQ0UgWU9VUiBPV04gTElDRU5TRSBIRVJFClRoaXMgc2FtcGxlIGxpY2Vuc2UgaXMgcHJvdmlkZWQgZm9yIGluZm9ybWF0aW9uYWwgcHVycG9zZXMgb25seS4KCk5PTi1FWENMVVNJVkUgRElTVFJJQlVUSU9OIExJQ0VOU0UKCkJ5IHNpZ25pbmcgYW5kIHN1Ym1pdHRpbmcgdGhpcyBsaWNlbnNlLCB5b3UgKHRoZSBhdXRob3Iocykgb3IgY29weXJpZ2h0Cm93bmVyKSBncmFudHMgdG8gRFNwYWNlIFVuaXZlcnNpdHkgKERTVSkgdGhlIG5vbi1leGNsdXNpdmUgcmlnaHQgdG8gcmVwcm9kdWNlLAp0cmFuc2xhdGUgKGFzIGRlZmluZWQgYmVsb3cpLCBhbmQvb3IgZGlzdHJpYnV0ZSB5b3VyIHN1Ym1pc3Npb24gKGluY2x1ZGluZwp0aGUgYWJzdHJhY3QpIHdvcmxkd2lkZSBpbiBwcmludCBhbmQgZWxlY3Ryb25pYyBmb3JtYXQgYW5kIGluIGFueSBtZWRpdW0sCmluY2x1ZGluZyBidXQgbm90IGxpbWl0ZWQgdG8gYXVkaW8gb3IgdmlkZW8uCgpZb3UgYWdyZWUgdGhhdCBEU1UgbWF5LCB3aXRob3V0IGNoYW5naW5nIHRoZSBjb250ZW50LCB0cmFuc2xhdGUgdGhlCnN1Ym1pc3Npb24gdG8gYW55IG1lZGl1bSBvciBmb3JtYXQgZm9yIHRoZSBwdXJwb3NlIG9mIHByZXNlcnZhdGlvbi4KCllvdSBhbHNvIGFncmVlIHRoYXQgRFNVIG1heSBrZWVwIG1vcmUgdGhhbiBvbmUgY29weSBvZiB0aGlzIHN1Ym1pc3Npb24gZm9yCnB1cnBvc2VzIG9mIHNlY3VyaXR5LCBiYWNrLXVwIGFuZCBwcmVzZXJ2YXRpb24uCgpZb3UgcmVwcmVzZW50IHRoYXQgdGhlIHN1Ym1pc3Npb24gaXMgeW91ciBvcmlnaW5hbCB3b3JrLCBhbmQgdGhhdCB5b3UgaGF2ZQp0aGUgcmlnaHQgdG8gZ3JhbnQgdGhlIHJpZ2h0cyBjb250YWluZWQgaW4gdGhpcyBsaWNlbnNlLiBZb3UgYWxzbyByZXByZXNlbnQKdGhhdCB5b3VyIHN1Ym1pc3Npb24gZG9lcyBub3QsIHRvIHRoZSBiZXN0IG9mIHlvdXIga25vd2xlZGdlLCBpbmZyaW5nZSB1cG9uCmFueW9uZSdzIGNvcHlyaWdodC4KCklmIHRoZSBzdWJtaXNzaW9uIGNvbnRhaW5zIG1hdGVyaWFsIGZvciB3aGljaCB5b3UgZG8gbm90IGhvbGQgY29weXJpZ2h0LAp5b3UgcmVwcmVzZW50IHRoYXQgeW91IGhhdmUgb2J0YWluZWQgdGhlIHVucmVzdHJpY3RlZCBwZXJtaXNzaW9uIG9mIHRoZQpjb3B5cmlnaHQgb3duZXIgdG8gZ3JhbnQgRFNVIHRoZSByaWdodHMgcmVxdWlyZWQgYnkgdGhpcyBsaWNlbnNlLCBhbmQgdGhhdApzdWNoIHRoaXJkLXBhcnR5IG93bmVkIG1hdGVyaWFsIGlzIGNsZWFybHkgaWRlbnRpZmllZCBhbmQgYWNrbm93bGVkZ2VkCndpdGhpbiB0aGUgdGV4dCBvciBjb250ZW50IG9mIHRoZSBzdWJtaXNzaW9uLgoKSUYgVEhFIFNVQk1JU1NJT04gSVMgQkFTRUQgVVBPTiBXT1JLIFRIQVQgSEFTIEJFRU4gU1BPTlNPUkVEIE9SIFNVUFBPUlRFRApCWSBBTiBBR0VOQ1kgT1IgT1JHQU5JWkFUSU9OIE9USEVSIFRIQU4gRFNVLCBZT1UgUkVQUkVTRU5UIFRIQVQgWU9VIEhBVkUKRlVMRklMTEVEIEFOWSBSSUdIVCBPRiBSRVZJRVcgT1IgT1RIRVIgT0JMSUdBVElPTlMgUkVRVUlSRUQgQlkgU1VDSApDT05UUkFDVCBPUiBBR1JFRU1FTlQuCgpEU1Ugd2lsbCBjbGVhcmx5IGlkZW50aWZ5IHlvdXIgbmFtZShzKSBhcyB0aGUgYXV0aG9yKHMpIG9yIG93bmVyKHMpIG9mIHRoZQpzdWJtaXNzaW9uLCBhbmQgd2lsbCBub3QgbWFrZSBhbnkgYWx0ZXJhdGlvbiwgb3RoZXIgdGhhbiBhcyBhbGxvd2VkIGJ5IHRoaXMKbGljZW5zZSwgdG8geW91ciBzdWJtaXNzaW9uLgo=