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26.06.2019 | PRECLINICAL STUDIES Open Access

Anticancer activity of a novel methylated analogue of L-mimosine against an in vitro model of human malignant melanoma

Investigational New Drugs
Sotiris Kyriakou, Melina Mitsiogianni, Theodora Mantso, William Cheung, Stephen Todryk, Stephany Veuger, Aglaia Pappa, David Tetard, Mihalis I. Panayiotidis
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The online version of this article (https://​doi.​org/​10.​1007/​s10637-019-00809-0) contains supplementary material, which is available to authorized users.

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The anticancer activity of a series of novel synthesized, hydroxypyridone-based metal chelators (analogues of L-mimosine) was evaluated in an in vitro model of melanoma consisting of malignant melanoma (A375), non-melanoma epidermoid carcinoma (A431) and immortalized non-malignant keratinocyte (HaCaT) cells. More specifically, we have demonstrated that the L-enantiomer of a methylated analogue of L-mimosine (compound 22) can exert a potent anticancer effect in A375 cells when compared to either A431 or HaCaT cells. Moreover, we have demonstrated that this analogue has the ability to i) promote increased generation of reactive oxygen species (ROS), ii) activate both intrinsic and extrinsic apoptosis and iii) induce perturbations in cell cycle growth arrest. Our data highlights the potential of compound 22 to act as a promising therapeutic agent against an in vitro model of human malignant melanoma.

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ESM 1 Additional figures illustrating purity data; (HPLC chromatographs), structure verification; 1H-NMR, 13C-NMR and HRMS spectra for all the intermediates and final products generated in this study. This material is available to authorized users. (PDF 4717 kb)
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