Repository logo
 
Publication

Synthesis, structural characterization and leishmanicidal activity evaluation of ferrocenyl N-heterocyclic compounds

2013-11-15Journal article Restricted access
Simple item page
dc.contributor.authorQuintal, Susana
dc.contributor.authorMorais, Tânia S.
dc.contributor.authorMatos, Cristina P.
dc.contributor.authorRobalo, Maria Paula
dc.contributor.authorPiedade, M. Fátima M.
dc.contributor.authorBrito, Maria J. Villa de
dc.contributor.authorGarcia, M. Helena
dc.contributor.authorMarques, Mónica
dc.contributor.authorMaia, Carla
dc.contributor.authorCampino, Lenea
dc.contributor.authorMadureira, João
dc.date.accessioned2014-09-16T19:26:14Z
dc.date.available2014-09-16T19:26:14Z
dc.date.issued2013-11-15
dc.descriptionAgência Financiadora: FCT - PTDC/QUI/72656/2006 ; SFRH/BPD/27454/2006; SFRH/BPD/44082/2008; SFRH/BPD/41138/2007por
dc.description.abstractNew ferrocenyl derivatives with the general formula FcC(O)L [Fc = (eta(5)-C5H5)Fe(eta(5)-C5H4)], where L is an aminoquinoline or hydroxyaminoquinoline, have been synthesized for evaluation of their leishmanicidal properties. The compounds were designed with ferrocene coupled to the quinolines by an amide or ester bridge. Ferrocenyl component is intended to act as quinoline carrier and ROS producer after in vivo oxidation to Fe(III), while decreasing normal cell cytotoxicity of coupled quinolines. The bridge was chosen based on its known ability to undergo hydrolysis by the protease/esterase rich media in phagolysosomes, the target of the intracellular form of leishmania parasites. The new compounds include N-(quinolin-3-yl)ferrocenamide (4), N-(quinolin-5-yl)ferrocenamide (5), N-(quinolin-6-yl)ferrocenamide (6), N-(2-methyl-quinolin-4-yl)ferrocenamide (7), N-(2-methylquinolin-6yl)ferrocenamide (8), N-(6-methoxy-quinolin-8-yl)ferrocenamide (9), 2-amino-quinolin-8-yl ferrocenoate (10) and 2-amino-quinolin-4-yl ferrocenoate (11). They were characterized by NMR, cyclic voltammetry, mass spectrometry, UV/vis, FT-IR and elemental analysis, which confirmed all the proposed molecular structures. Compounds 7 and 8 were also structurally characterized by single crystal X-ray diffraction. In 7, the 4-amino-2-methylquinoline moiety is perpendicular to the substituted cyclopentadienyl ring (Cp), while in 8 the 6-amino-2-methylquinoline component is coplanar to the substituted Cp. The new compounds (4-11), same as four other previously published (1-ferrocenoyl-1H-(2-aminobenzimidazole) (1), 1-ferrocenoyl-1H-benzimidazole (2), 1-ferrocenoyl-1H-imidazole (3) and N-(pyridin-4-yl)ferrocenamide (12)), were evaluated in vitro in cultures of a Leishmania infantum strain, isolated from a human visceral leishmaniasis case, to establish their leishmanicidal activity. The toxicity against the human caucasian histiocytic lymphoma U-937 cell line was analyzed for the same set of compounds. All of them show activity against promastigote forms of L. infantum parasites at relatively high concentration (64-269 mu M). Among the complexes that showed a better ratio between the toxic and the therapeutic dose, 3, 9 and 12 were selected for further studies in infected macrophages. Such compounds showed a very significant increase in their activity (17-23 times) giving very similar IC50 values (5.2-5.7 mu M). All three compounds gave significantly better therapeutic indexes (88.5, 12; 56.4, 3; 16.6, 9) than the control miltefosine (6.1).(2) (C) 2013 Elsevier B.V. All rights reserved.por
dc.identifier.citationQUINTAL, Susana; [et al] - Synthesis, structural characterization and leishmanicidal activity evaluation of ferrocenyl N-heterocyclic compounds. Journal of Organometallic Chemistry. Vol. 745 (2013), p. 299-311.por
dc.identifier.doi10.1016/j.jorganchem.2013.07.044
dc.identifier.issn0022-328X
dc.identifier.issn1872-8561
dc.identifier.urihttp://hdl.handle.net/10400.21/3810
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherElsevier Science SApor
dc.relation.publisherversionhttp://www.sciencedirect.com/science/article/pii/S0022328X13005512por
dc.subjectFerrocenylpor
dc.subjectAmidepor
dc.subjectEsterpor
dc.subjectN-Heterocyclepor
dc.subjectLeishmanicidal activitypor
dc.titleSynthesis, structural characterization and leishmanicidal activity evaluation of ferrocenyl N-heterocyclic compoundspor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceLausannepor
oaire.citation.endPage311por
oaire.citation.startPage299por
oaire.citation.titleJournal of Organometallic Chemistrypor
oaire.citation.volume745por
person.familyNameRobalo
person.familyNameAnselmo Viegas Garcia
person.familyNameCampino
person.givenNameMaria Paula
person.givenNameMaria Helena
person.givenNameLenea
person.identifierH-2175-­2013
person.identifier.ciencia-idE11C-A704-9C18
person.identifier.ciencia-id5414-9AEF-4194
person.identifier.ciencia-id2A16-58CC-48FE
person.identifier.orcid0000-0002-8200-6910
person.identifier.orcid0000-0002-4344-2218
person.identifier.orcid0000-0003-4512-9660
person.identifier.ridB-2002-2012
person.identifier.scopus-author-id9269662100
person.identifier.scopus-author-id6507884466
person.identifier.scopus-author-id6603808132
rcaap.rightsrestrictedAccesspor
rcaap.typearticlepor
relation.isAuthorOfPublication823a9498-17ab-451f-bb8f-56338643ac0c
relation.isAuthorOfPublicationddef2398-fb7d-4551-a9fe-71c411d1d706
relation.isAuthorOfPublication43833249-85f0-417e-901b-0c78ca6f2329
relation.isAuthorOfPublication.latestForDiscovery823a9498-17ab-451f-bb8f-56338643ac0c

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
Synthesis, structural characterization and leishmanicidal activity evaluation of ferrocenyl N-heterocyclic compounds.pdf
Size:
941.48 KB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

ISEL - Eng. Quim. Biol. - Artigos