dc.contributor.author | Horta, Pedro | |
dc.contributor.author | Kuş, Nihal | |
dc.contributor.author | Henriques, Marta Sofia C. | |
dc.contributor.author | Paixao, Jose A. | |
dc.contributor.author | Coelho, Lis | |
dc.contributor.author | Nogueira, Fatima | |
dc.contributor.author | Santos Cristiano, Maria Lurdes | |
dc.date.accessioned | 2019-10-20T09:13:34Z | |
dc.date.available | 2019-10-20T09:13:34Z | |
dc.date.issued | 2015 | |
dc.identifier.issn | 0022-3263 | |
dc.identifier.uri | https://dx.doi.org/10.1021/acs.joc.5b02169 | |
dc.identifier.uri | https://hdl.handle.net/11421/16972 | |
dc.description | WOS: 000366877900036 | en_US |
dc.description | PubMed ID: 26551438 | en_US |
dc.description.abstract | Recent publications report in vitro activity of quinolone 3-esters against the bc(1) protein complex of Plasmodium falciparum and the parasite. Docking studies performed in silica at the yeast Q(o) Site established a key role for the 4-oxo and N-H groups in drug-target interactions. Thus, the possibility of 4-oxoquinoline/4-hydroxyquinoline tautomerism may impact in pharmacologic profiles and should be investigated. We describe the synthesis, structure, photochemistry, and activity against multidrug-resistant P. falciparum strain Dd2 of ethyl 4-oxo-7-methylquinoline-3-carboxylate (7Me-OQE) and ethyl 4-hydroxy-5-methylquinoline-3-carboxylate (5Me-HQE), obtained from diethyl 2-[((3-methylphenyl)amino)methylene]malonate. Theoretically (B3LYP/6-311+ +G(d,p)), 5Me-HQE and 7Me-OQE show clear preference for the hydroxyquinoline form. The difference between the lowest energy hydroxyquinoline and quinolone forms is 27 and 38 kJ mol(-1), for 5Me-HQE and 7Me-OQE, respectively. Calculations of atomaticity indexes show that in 5Me-HQE,both rings are aromatic, while in the corresponding oxo tautomers the nitrogen-containing ring is essentially non-aromatic. The structure of monomeric 5Me-HQE was studied using matrix-isolation coupled to FTIR spectroscopy. No traces of 4-oxoquinoline tautomers were found in the experimental IR spectra, revealing that:the species present in the crystal, 5Me-HQE center dot HCl, was lost HCl upon sublimation but did not tautomerize. Continuous broadband irradiation (lambda > 220 nm; 130 min) of the matrix led to only partial photodecomposition of 5Me-HQE (ca. 1/3). | en_US |
dc.description.sponsorship | Fundacao para a Ciencia e a Tecnologia (FCT), Portugal [PEst-C/MAR/LA0015/603 2013]; QREN-COMPETE-UE; CCMAR; FCT [PEst-OE/QUI/UI0313/2014, SFRH/BD/81821/2011, SFRH/BPD/88372/2012]; Engineering and Physical Sciences Research Council [EP/K039687/1] | en_US |
dc.description.sponsorship | The authors gratefully acknowledge Fundacao para a Ciencia e a Tecnologia (FCT), Portugal (Project PEst-C/MAR/LA0015/603 2013), cofounded by QREN-COMPETE-UE and CCMAR for generous financial support. The Coimbra Chemistry Centre (CQC) is also supported by FCT through Project PEst-OE/QUI/UI0313/2014. P.H. acknowledges FCT for the award of a doctoral grant (SFRH/BD/81821/2011). N.K acknowledges FCT for the award of a postdoctoral grant (SFRH/BPD/88372/2012). NMR spectrometers used are part of The National NMR Facility, supported by Fundacao para a Ciencia e a Tecnologia (RECI/BBB-BQB/0230/2012). | en_US |
dc.language.iso | eng | en_US |
dc.publisher | American Chemical Society | en_US |
dc.relation.isversionof | 10.1021/acs.joc.5b02169 | en_US |
dc.rights | info:eu-repo/semantics/closedAccess | en_US |
dc.title | Quinolone-Hydroxyquinoline Tautomerism in Quinolone 3-Esters. Preserving the 4-Oxoquinoline Structure To Retain Antimalarial Activity | en_US |
dc.type | article | en_US |
dc.relation.journal | Journal of Organic Chemistry | en_US |
dc.contributor.department | Anadolu Üniversitesi, Fen Fakültesi, Fizik Bölümü | en_US |
dc.identifier.volume | 80 | en_US |
dc.identifier.issue | 24 | en_US |
dc.identifier.startpage | 12244 | en_US |
dc.identifier.endpage | 12257 | en_US |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | en_US |
dc.contributor.institutionauthor | Kuş, Nihal | |