Antiparasitic activity of new gibbilimbol analogues and SAR analysis through efficiency and statistical methods

Imagem de Miniatura
Arquivos
art_VARELA_Antiparasitic_activity_of_new_gibbilimbol_analogues_and_SAR_2018.PDF (1.18 MB)
Citações na Scopus
13
Tipo de produção
article
Data de publicação
2018
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
ELSEVIER SCIENCE BV
Autores
VARELA, Marina T.
ROMANELI, Maiara M.
BORBOREMA, Samanta E. T.
TEMPONE, Andre G.
FERNANDES, Joao P. S.
Citação
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, v.122, p.31-41, 2018
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Chagas' disease and leishmaniasis are parasitic infections enrolled among the neglected tropical diseases, which urge for new treatments. In the search for new chemical entities as prototypes, gibbilimbols A/B have shown antiparasitic activity against Trypanosoma cruzi and Leishmania infantum, and then a set of analogues (LINS03 series) of this natural product were synthesized and evaluated in vitro against the parasites. In the present paper we reported five new compounds with activity against these protozoan parasites, and quite low cytotoxicity. Moreover, the interference of plasma membrane permeability of these analogues were also evaluated. We found that [(4-methoxyphenyl) methyl] octylamine (4) was noteworthy due to its high activity against the amastigote form of both parasites (IC50 1.3-5.8 mu M) and good selectivity index. In order to unveil the SAR for this chemotype, we also presented a group efficiency analysis and PCA and HCA study, which indicated that the methoxyl provides good activity with lower cytotoxicity to mammalian cells. The results from SAR analyses suggest different mechanisms of action between the neutral and basic compounds. In summary, the analogues represent important activity against these parasites and must be prototypes for further exploitation.
Palavras-chave
Anti-trypanosoma, Group efficiency, Leishmanicide, Natural product analogues, SAR analysis
URI
https://observatorio.fm.usp.br/handle/OPI/28511
Referências
  1. Ali MA, 2014, TETRAHEDRON LETT, V55, P1316, DOI 10.1016/j.tetlet.2013.12.111
  2. Atanasov AG, 2015, BIOTECHNOL ADV, V33, P1582, DOI 10.1016/j.biotechadv.2015.08.001
  3. BARRY J, 1985, SYNTHESIS-STUTTGART, P40
  4. Bartzatt R, 2017, J PHARM BIOL SCI, V12, P144
  5. Castillo JC, 2016, EUR J ORG CHEM, P3824, DOI 10.1002/ejoc.201600549
  6. ChemAxon Inc, 2016, MARVINBEANS 16 8 1 0
  7. De Oliveira A, 2012, EXP PARASITOL, V132, P383, DOI 10.1016/j.exppara.2012.08.019
  8. Ferreira João E. V., 2014, Educ. quím, V25, P418
  9. Gimenez BG, 2010, PHARMAZIE, V65, P148, DOI 10.1691/ph.2010.9733
  10. Griffin W., 1949, J SOC COSMET CHEM, V1, P311, DOI 10.1007/BFB0117162
  11. HAMMER O., 2001, PALAEONTOL ELECTRON, V4, P1, DOI 10.1016/J.BCP.2008.05.025
  12. Harvey AL, 2015, NAT REV DRUG DISCOV, V14, P111, DOI 10.1038/nrd4510
  13. Hopkins AL, 2014, NAT REV DRUG DISCOV, V13, P105, DOI 10.1038/nrd4163
  14. Katsuno K, 2015, NAT REV DRUG DISCOV, V14, P751, DOI 10.1038/nrd4683
  15. Kubinyi H, 1993, QSAR HANSCH ANAL REL
  16. Lipinski CA, 2001, ADV DRUG DELIVER REV, V46, P3, DOI 10.1016/S0169-409X(00)00129-0
  17. Martins LF, 2016, J NAT PROD, V79, P2202, DOI 10.1021/acs.jnatprod.6b00256
  18. McGwire BS, 2014, QJM-INT J MED, V107, P7, DOI 10.1093/qjmed/hct116
  19. Molinspiration Cheminformatics, 2015, CAL MOL PROP BIOACT
  20. PEARL IA, 1951, J AM CHEM SOC, V73, P4091, DOI 10.1021/ja01153a011
  21. Nunes MCP, 2013, J AM COLL CARDIOL, V62, P767, DOI 10.1016/j.jacc.2013.05.046
  22. Reimao JQ, 2012, EXP PARASITOL, V130, P195, DOI 10.1016/j.exppara.2012.01.010
  23. Reimao JQ, 2008, PARASITOL RES, V103, P1445, DOI 10.1007/s00436-008-1154-6
  24. Luque-Ortega JR, 2010, METHODS MOL BIOL, V618, P393, DOI 10.1007/978-1-60761-594-1_25
  25. SCHULTES S, 2010, DRUG DISCOV TODAY TE, V7, pE147, DOI 10.1016/j.ddtec.2010.11.003
  26. Trouiller P, 2002, LANCET, V359, P2188, DOI 10.1016/S0140-6736(02)09096-7
  27. Utzinger J, 2012, SWISS MED WKLY, V142, DOI 10.4414/smw.2012.13727
  28. van den Berg RA, 2006, BMC GENOMICS, V7, DOI 10.1186/1471-2164-7-142
  29. Varela MT, 2017, CHEM BIOL DRUG DES, V90, P1007, DOI 10.1111/cbdd.12986
  30. Varela MT, 2016, BIOORG MED CHEM LETT, V26, P1180, DOI 10.1016/j.bmcl.2016.01.040
  31. Veber DF, 2002, J MED CHEM, V45, P2615, DOI 10.1021/jm020017n
  32. Vendrame R, 2002, J MOL GRAPH MODEL, V20, P345, DOI 10.1016/S1093-3263(01)00107-3
  33. Verdonk ML, 2008, CHEMMEDCHEM, V3, P1179, DOI 10.1002/cmdc.200800132
  34. WARD JH, 1963, J AM STAT ASSOC, V58, P236, DOI 10.2307/2282967
  35. WHO (World and Health Organization), 2017, NEGLECTED TROPICAL D

Coleções
Artigos e Materiais de Revistas Científicas - IMT
Artigos e Materiais de Revistas Científicas - ODS/03