Jump to main content
Jump to site search

Issue 5, 2015
Previous Article Next Article

1,2,3-Dithiazoles – new reversible melanin synthesis inhibitors: a chemical genomics study

Author affiliations

Abstract

A chemical genomic screen of an in-house library of small molecule heterocycles was carried out using Xenopus laevis embryos. This led to the identification of N-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)-4-methoxyaniline (1c), which elicits loss of pigmentation in melanophores and the retinal pigment epithelium (RPE) of developing embryos, independent of the developmental stage of initial exposure. The phenotype was reversible, since pigmentation returned upon compound removal while analysis of neural crest cell markers (Pax7) and melanophore markers (Dct/Xtrp2) revealed that both neural crest precursors and fully differentiated melanophores were present in the dithiazole 1c treated embryos. A subsequent focused structure–activity relationship (SAR) study identified the more active dithiazole 4-benzyloxy-N-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)-aniline (1l) and the need for a chlorine substituent at the dithiazole C-4 position. Both the initial chemical genomic screen and the focused SAR study highlighted the toxicity of (dithiazolylidene)aminoazines, and also of methoxyaniline (anisidine) analogues that hosted strong electron-withdrawing or electronegative substituents or acidic hydroxyl groups on the anisidine moiety. This study suggests that 1,2,3-dithiazoles can act as reversible melanin synthesis inhibitors, revealing a new biological activity for this class of compounds. The inhibition of melanin synthesis is medically relevant as a potential treatment for pigmentation disorders such as melasma.

Graphical abstract: 1,2,3-Dithiazoles – new reversible melanin synthesis inhibitors: a chemical genomics study

Back to tab navigation

Article information


Submitted
06 Feb 2015
Accepted
26 Mar 2015
First published
31 Mar 2015

, 2015,6, 935-946
Article type
Concise Article

1,2,3-Dithiazoles – new reversible melanin synthesis inhibitors: a chemical genomics study

A. Charalambous, M. Koyioni, I. Antoniades, D. Pegeioti, I. Eleftheriou, S. S. Michaelidou, S. A. Amelichev, L. S. Konstantinova, O. A. Rakitin, P. A. Koutentis and P. A. Skourides, , 2015, 6, 935
DOI: 10.1039/C5MD00052A

Search articles by author

Spotlight

Advertisements