Liquid chromatography-electrospray ionization-tandem mass spectrometry method for quantitative estimation of new imiqualine leads with potent anticancer activities in rat and mouse plasma. Application to a pharmacokinetic study in mice

Chouchou, Adrien; Marion, Blandine; Enjalbal, Christine; Roques, Céline; Cuq, Pierre; Bonnet, Pierre-Antoine; Bressolle-Gomeni, Françoise; Deleuze‐Masquéfa, Carine

doi:10.1016/j.jpba.2017.10.025

Cited by 2 publications

(1 citation statement)

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“…Indeed, their low solubility in water might be a major drawback for further development, especially in the case of intravenous use. In a preliminary study [ 12 ], the pharmacokinetic parameters of EAPB02303 were determined in mice after a single intraperitoneal administration. For this, the compound was solubilized in a mixture of DMSO, Tween 80 and sodium chloride solution 0.9% (10/10/80, v / v / v ).…”

Section: Introductionmentioning

confidence: 99%

Imidazo[1,2-a]quinoxalines Derivatives Grafted with Amino Acids: Synthesis and Evaluation on A375 Melanoma Cells

et al. 2018

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Imiqualines (imidazoquinoxaline derivatives) are anticancer compounds with high cytotoxic activities on melanoma cell lines. The first generation of imiqualines, with two lead compounds (EAPB0203 and EAPB0503), shows remarkable in vitro (IC50 = 1 570 nM and IC50 = 200 nM, respectively, on the A375 melanoma cell line) and in vivo activity on melanoma xenografts. The second generation derivatives, EAPB02302 and EAPB02303, are more active, with IC50 = 60 nM and IC50 = 10 nM, respectively, on A375 melanoma cell line. The aim of this study was to optimize the bioavailability of imiqualine derivatives, without losing their intrinsic activity. For that, we achieved chemical modulation on the second generation of imiqualines by conjugating amino acids on position 4. A new series of twenty-five compounds was efficiently synthesized by using microwave assistance and tested for its activity on the A375 cell line. In the new series, compounds 11a, 9d and 11b show cytotoxic activities less than second generation compounds, but similar to that of the first generation ones (IC50 = 403 nM, IC50 = 128 nM and IC50 = 584 nM, respectively). The presence of an amino acid leads to significant enhancement of the water solubility for improved drugability.

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Section: Introductionmentioning

confidence: 99%