Molecular modeling of the voltammetric oxidation at a glassy carbon electrode of the antimalarial drug primaquine and its prodrugs succinylprimaquine and maleylprimaquine

La-Scalea, Mauro Aquiles; Menezes, Carla M. S.; Matsutami, Guilherme C.; Polli, Michelle Carneiro; Serrano, Sı́lvia Helena Pires; Ferreira, Elizabeth Igne

doi:10.1016/j.electacta.2006.03.085

Cited by 14 publications

(13 citation statements)

References 22 publications

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“…Molecular modification contributed to facilitate the drug electro-oxidation, but no biological assays of these potential prodrugs have been described [196].…”

Section: Modifications At the Terminal Primary Aminementioning

confidence: 99%

Primaquine revisited six decades after its discovery

Vale¹,

Moreira²,

Gomes³

2009

European Journal of Medicinal Chemistry

322

308

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“…Molecular modification contributed to facilitate the drug electro-oxidation, but no biological assays of these potential prodrugs have been described [196].…”

Section: Modifications At the Terminal Primary Aminementioning

confidence: 99%

Primaquine revisited six decades after its discovery

Vale¹,

Moreira²,

Gomes³

2009

European Journal of Medicinal Chemistry

322

308

View full text Add to dashboard Cite

“…The diverse analytical methods focused on the antimalarial primaquine (PQ, 1, Scheme 1) or its analogues have been so far targeted at pharmacokinetics studies and metabolite analysis [1][2][3][4][5][6][7][8][9] or isomer separation/characterization [10,11]. The application of molecular modeling studies associated to voltammetric techniques showed to be an important way to understand the redox mechanism of electro-active drugs where aminoquinolines (AQs) such as PQ are included [7].…”

Section: Introductionmentioning

confidence: 99%

“…The application of molecular modeling studies associated to voltammetric techniques showed to be an important way to understand the redox mechanism of electro-active drugs where aminoquinolines (AQs) such as PQ are included [7]. Two classes of AQs were investigated by infrared spectrometry to assess their geometry and coordination ability [6].…”

Section: Introductionmentioning

confidence: 99%

Characterization of primaquine imidazolidin-4-ones with antimalarial activity by electrospray ionization-ion trap mass spectrometry

Vale

Moreira

Gomes

2008

International Journal of Mass Spectrometry

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The extensive characterization by electrospray ionization-ion trap mass spectrometry (ESI-MS n ) of 20 imidazolidin-4-ones derived from the antimalarial primaquine was well obtained. These compounds are being under investigation as potential antimalarials, as they have been previously found to be active against rodent P. berghei malaria and to be highly stable under physiological conditions. Experiments by collision-induced dissociation (CID) in the nozzle-skimmer region or by tandem-MS have shown the title compounds to be remarkably stable. Mechanisms are proposed to explain the major fragmentations observed in ESI-MS n experiments. Overall, this work represents an unprecedented contribution to a deeper insight into imidazolidin-4-one antimalarials based on a classic 8-aminoquinolinic scaffold. Data herein reported and discussed may be an useful guide for future studies on therapeutically relevant molecules possessing either the 8-aminoquinoline or the imidazolidin-4-one motifs.

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“…Notwithstanding, little has been done on the application of this technique to the study of relevant antimalarials such as primaquine (PQ, 1) or related structures. Analytical methods focused on PQ or its analogues have been so far applied to pharmacokinetics studies and metabolite scrutiny [29][30][31][32][33][34][35][36][37] or isomer characterization [38,39]. Examples of mass spectrometry techniques employed to the study/analysis of PQ and related compounds include fast atom bombardment mass spectral (FAB-MS) analysis of PQ oxidation products [32] and supercritical fluid chromatography-mass spectrometry (SFC-MS) used to elucidate differences in the MS fragmentation patterns of PQ (free base), PQ diphosphate and its positional isomer quinocide and to achieve good resolution between these three compounds in short analysis times [36].…”

mentioning

confidence: 99%

Electrospray ionization-ion trap mass spectrometry study of PQAAPro and PQProAA mimetic derivatives of the antimalarial primaquine

Vale

Matos

Moreira

et al. 2008

J. Am. Soc. Mass Spectrom.

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Electrospray ionization-ion trap mass spectrometry (ESI-MS) of imidazolidin-4-one peptidemimetic derivatives of the antimalarial drug primaquine (PQ) is reported. These compounds contain the imidazolidin-4-one moiety either at the N-or the C-terminal of a dipeptide backbone, thus respectively mimicking PQ-Amino Acid-Proline (PQAAPro) and PQProAA derivatives of PQ. Both the peptidomimetics and precursors previously developed by us are promising drug candidates, as they were found to be active against rodent Plasmodium berghei malaria and Pneumocystis carinii pneumonia. Collision-induced dissociation (GD) and tandemmass spectra (MS) of the title compounds, and fragmentation pathways thereof, led to the following findings: (1) CID patterns present some parallelism with the reactivity towards hydrolysis previously found for the same or related compounds; (2) a positional shift of the imidazolidin-d-one ring is reflected on both degree and pathways of fragmentation, which makes tandem-MS a key tool for differentiation of imidazolidin-i-one isomers; (3) the major MS/MS fragmentation of PQProAA mimetics involves release of a neutral diketopiperazine (DKP), in parallel to the "diketopiperazine pathway" described in tandem-MS studies of oligopeptides; (4) the relative abundance of a major fragment in tandem-MS spectra is inversely correlated with the size of the N-terminal AA in PQProAA mimetics. Overall, this work embodies an original and valuable contribution towards a deeper insight into the molecular properties of novel antimalarials, which can be viewed as representative of both the 8-aminoquinoline and, especially, the imidazolidin-4-one structural classes. aAm Soc Mass Spectrom 2008, 19, 1476-1490 ) © 2008 American Society for Mass SpectrometryO ver the past decade, electrospray ionization mass spectrometry (ESI-MS) has been used for the most diverse analytical purposes. This technique has provided deeper insight into the structural properties and stability of numerous compounds, from natural products [1-3] to synthetic drugs [4-8], peptides [9-23], and heterocycles [24][25][26][27][28], among many others. Notwithstanding, little has been done on the application of this technique to the study of relevant antimalarials such as primaquine (PQ, 1) or related structures. Analytical methods focused on PQ or its analogues have been so far applied to pharmacokinetics studies and metabolite scrutiny [29][30][31][32][33][34][35][36][37] or isomer characterization [38,39]. Examples of mass spectrometry techniques employed to the study/analysis of PQ and related compounds include fast atom bombardment mass spectral (FAB-MS) analysis of PQ oxidation products [32] and supercritical fluid chromatography-mass Address reprint requests to Dr. P.

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Molecular modeling of the voltammetric oxidation at a glassy carbon electrode of the antimalarial drug primaquine and its prodrugs succinylprimaquine and maleylprimaquine

Cited by 14 publications

References 22 publications

Primaquine revisited six decades after its discovery

Primaquine revisited six decades after its discovery

Characterization of primaquine imidazolidin-4-ones with antimalarial activity by electrospray ionization-ion trap mass spectrometry

Electrospray ionization-ion trap mass spectrometry study of PQAAPro and PQProAA mimetic derivatives of the antimalarial primaquine

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