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Molecules 2018, 23(11), 2987; https://doi.org/10.3390/molecules23112987

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

1
IBMM, Université de Montpellier, CNRS, ENSCM, 34000 Montpellier, France
2
Société d’Accélération du Transfert de Technologies (SATT AxLR), CSU, 950 rue Saint Priest, 34090 Montpellier, France
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 30 October 2018 / Revised: 10 November 2018 / Accepted: 13 November 2018 / Published: 15 November 2018
(This article belongs to the Section Medicinal Chemistry)
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Abstract

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. View Full-Text
Keywords: imidazo[1,2-a]quinoxaline; melanoma; imiqualine; A375 structure–activity relationship imidazo[1,2-a]quinoxaline; melanoma; imiqualine; A375 structure–activity relationship
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Chouchou, A.; Patinote, C.; Cuq, P.; Bonnet, P.-A.; Deleuze-Masquéfa, C. Imidazo[1,2-a]quinoxalines Derivatives Grafted with Amino Acids: Synthesis and Evaluation on A375 Melanoma Cells. Molecules 2018, 23, 2987.

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