Designed benzothiadiazole fluorophores for selective mitochondrial imaging and dynamics.

Abstract

A series of new rationale designed 2,1,3-benzothiadiazole (BTD) fluorescent derivatives has been synthesized and applied for cellular selective staining of cancer cells in cell-imaging experiments. Four new synthesized BTD derivatives showed only poor or reasonable cellular selection, but with excellent fluorescence intensity and almost no background signal emitting at the blue or green channels. The knowledge gained by analysing their molecular architecture, however, allowed the planning and synthesis of a fluorescent BTD, which was then successfully tested and showed superior mitochondrial selection with outstanding results in bioimaging experiments in living cells. The new marker (named Splendor) was then compared with the commercially available MitoTracker Red (also through co-staining experiments) and showed far better mitochondrial selection, fluorescence intensity and chemical stability. Mitochondrial imaging and tracking (dynamic changes) was possible using Splendor during the whole cellular division cycle. DFT calculations were performed to offer insights into the origin of the chemical- and photostability of BTD derivatives. In addition, molecular docking calculations hint at a potential molecular target for the BTD derivatives in the mitochondrial protein adenine nucleotide translocase, which may explain the mitochondrial selectivity of Splendor versus the other four BTD derivatives.

• Authors: Pedro H P R Carvalho, Jose R Correa, Bruna C Guido, Claudia C Gatto, Heibbe C B De Oliveira, Thereza A Soares, Brenno A D Neto
• Journal: Chemistry (Weinheim an der Bergstrasse, Germany) (Chemistry) Vol. 20 Issue 47 Pg. 15360-74 (Nov 17 2014) ISSN: 1521-3765 [Electronic] Germany
• PMID: 25335818 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Fluorescent Dyes
• Thiadiazoles
• benzo-1,2,3-thiadiazole

Topics

• Binding Sites
• Crystallography, X-Ray
• Fluorescent Dyes (chemical synthesis, chemistry, metabolism)
• Humans
• MCF-7 Cells
• Microscopy, Confocal
• Mitochondria (metabolism)
• Molecular Conformation
• Molecular Docking Simulation
• Quantum Theory
• Thiadiazoles (chemical synthesis, chemistry, metabolism)