Imidazo[1,2-<i>a</i>]quinoxalines Derivatives Grafted with Amino Acids: Synthesis and Evaluation on A375 Melanoma Cells
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 (IC<sub>50</sub> = 1 570 nM and IC<sub>50<...
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| Format: | Article |
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MDPI AG
2018-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/23/11/2987 |
| _version_ | 1819264482818392064 |
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| author | Adrien Chouchou Cindy Patinote Pierre Cuq Pierre-Antoine Bonnet Carine Deleuze-Masquéfa |
| author_facet | Adrien Chouchou Cindy Patinote Pierre Cuq Pierre-Antoine Bonnet Carine Deleuze-Masquéfa |
| author_sort | Adrien Chouchou |
| collection | DOAJ |
| description | 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 (IC<sub>50</sub> = 1 570 nM and IC<sub>50</sub> = 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 IC<sub>50</sub> = 60 nM and IC<sub>50</sub> = 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 <b>11a</b>, <b>9d</b> and <b>11b</b> show cytotoxic activities less than second generation compounds, but similar to that of the first generation ones (IC<sub>50</sub> = 403 nM, IC<sub>50</sub> = 128 nM and IC<sub>50</sub> = 584 nM, respectively). The presence of an amino acid leads to significant enhancement of the water solubility for improved drugability. |
| first_indexed | 2024-12-23T20:30:11Z |
| format | Article |
| id | doaj.art-1ffa6c3090ab47cd98c51f50d59e7d11 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-23T20:30:11Z |
| publishDate | 2018-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-1ffa6c3090ab47cd98c51f50d59e7d112022-12-21T17:32:16ZengMDPI AGMolecules1420-30492018-11-012311298710.3390/molecules23112987molecules23112987Imidazo[1,2-<i>a</i>]quinoxalines Derivatives Grafted with Amino Acids: Synthesis and Evaluation on A375 Melanoma CellsAdrien Chouchou0Cindy Patinote1Pierre Cuq2Pierre-Antoine Bonnet3Carine Deleuze-Masquéfa4IBMM, Université de Montpellier, CNRS, ENSCM, 34000 Montpellier, FranceIBMM, Université de Montpellier, CNRS, ENSCM, 34000 Montpellier, FranceIBMM, Université de Montpellier, CNRS, ENSCM, 34000 Montpellier, FranceIBMM, Université de Montpellier, CNRS, ENSCM, 34000 Montpellier, FranceIBMM, Université de Montpellier, CNRS, ENSCM, 34000 Montpellier, FranceImiqualines (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 (IC<sub>50</sub> = 1 570 nM and IC<sub>50</sub> = 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 IC<sub>50</sub> = 60 nM and IC<sub>50</sub> = 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 <b>11a</b>, <b>9d</b> and <b>11b</b> show cytotoxic activities less than second generation compounds, but similar to that of the first generation ones (IC<sub>50</sub> = 403 nM, IC<sub>50</sub> = 128 nM and IC<sub>50</sub> = 584 nM, respectively). The presence of an amino acid leads to significant enhancement of the water solubility for improved drugability.https://www.mdpi.com/1420-3049/23/11/2987imidazo[1,2-<i>a</i>]quinoxalinemelanomaimiqualineA375 structure–activity relationship |
| spellingShingle | Adrien Chouchou Cindy Patinote Pierre Cuq Pierre-Antoine Bonnet Carine Deleuze-Masquéfa Imidazo[1,2-<i>a</i>]quinoxalines Derivatives Grafted with Amino Acids: Synthesis and Evaluation on A375 Melanoma Cells Molecules imidazo[1,2-<i>a</i>]quinoxaline melanoma imiqualine A375 structure–activity relationship |
| title | Imidazo[1,2-<i>a</i>]quinoxalines Derivatives Grafted with Amino Acids: Synthesis and Evaluation on A375 Melanoma Cells |
| title_full | Imidazo[1,2-<i>a</i>]quinoxalines Derivatives Grafted with Amino Acids: Synthesis and Evaluation on A375 Melanoma Cells |
| title_fullStr | Imidazo[1,2-<i>a</i>]quinoxalines Derivatives Grafted with Amino Acids: Synthesis and Evaluation on A375 Melanoma Cells |
| title_full_unstemmed | Imidazo[1,2-<i>a</i>]quinoxalines Derivatives Grafted with Amino Acids: Synthesis and Evaluation on A375 Melanoma Cells |
| title_short | Imidazo[1,2-<i>a</i>]quinoxalines Derivatives Grafted with Amino Acids: Synthesis and Evaluation on A375 Melanoma Cells |
| title_sort | imidazo 1 2 i a i quinoxalines derivatives grafted with amino acids synthesis and evaluation on a375 melanoma cells |
| topic | imidazo[1,2-<i>a</i>]quinoxaline melanoma imiqualine A375 structure–activity relationship |
| url | https://www.mdpi.com/1420-3049/23/11/2987 |
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