Quinone-based fluorophores for imaging biological processes

Abstract

Quinones are privileged chemical structures playing crucial roles as redox and alkylating agents in a wide range of processes in cells. The broad functional array of quinones has prompted the development of new chemical approaches, including C-H bond activation and asymmetric reactions, to generate probes for examining their activity by means of fluorescence imaging. This tutorial review covers recent advances in the design, synthesis and applications of quinone-based fluorescent agents for visualizing specific processes in multiple biological systems, from cells to tissues and complex organisms in vivo.

Trimethyl Lock: A Multifunctional Molecular Tool for Drug Delivery, Cellular Imaging, and Stimuli‐Responsive Materials

“…These enzymes are involved in electron transportw ithin the respiratory chain and in photosynthesis in eukaryotes as well as prokaryotes. [7] Numerous quinone-TML-based prodrugs of anticancer compounds [e.g.,the VEGF-induced angiogenesis inhibitor semaxanib (58), the farnesyl transferase inhibitor preussomerin I( 60), the cytotoxin zerumbone (62), and antimitotic combretastatin sulfamide analogue 64,a nd nitrogen-lost 65,S cheme 13] have been developed and demonstrated to release their parent drug preferentially in the hypoxic tissue of certain cancert ypes overexpressing NQO1. [82] The quinone-oxidoreductase-mediated transformation of benzoquinone-type TML structures to their corresponding dihydroquinones can, therefore, trigger the release of compounds attachedt ot he carboxylic acid moiety.…”

“…[100] The authors demonstrate selective cytotoxicity of their conjugate towards the cancer cell lines A-549 and HeLa overexpressing biotin receptors compared to two healthy cell lines. [117,118] However,i nc oumarin-MTXp rodrug 82,t he photocleavability of the (coumarin-4-yl)methyl ester is locked by attachment of aq uinone-type TML moiety to the 7-hydroxy functionb ecause of resulting reductiveP eT [7] between the excited coumarin moiety and the quinone TMLp art. [100] Recently,W ua nd co-workersh ave reported aq uinone-type TML-based coumarin-methotrexate (MTX) prodrug designed for sequential enzyme-activateda nd light-triggered releaseo f the antimetabolite for cancer treatment.…”

“…[1][2][3] Similarly,i ti si mportant for prodrug strategies aiming to minimize systemic adverse effects and to improvet he pharmacokinetics of ac ompound. [7] In this context, ah ighly versatile molecular releases ystem is the "trimethyl lock" (TML) system, which is based on the increased lactonization reactivity of trimethylsubstituted ortho-hydroxydihydrocinnamic acid derivatives. [7] In this context, ah ighly versatile molecular releases ystem is the "trimethyl lock" (TML) system, which is based on the increased lactonization reactivity of trimethylsubstituted ortho-hydroxydihydrocinnamic acid derivatives.…”

“…[4][5][6] Furthermore, molecular systems able to release fluorescent molecules upon specific triggering can be appliedi nt he developmento fi maging tools in chemicalb iology. [8] TMLs have been adapted to av ariety of different chemical and enzymatic triggersa nd, therefore, have found av arietyo fa pplicationsi nm odern drug design,c ell imaging, [7] and the development of chemical tools, all of which were summarized in an excellent review by Levine and Rainesi n2 012. [8] TMLs have been adapted to av ariety of different chemical and enzymatic triggersa nd, therefore, have found av arietyo fa pplicationsi nm odern drug design,c ell imaging, [7] and the development of chemical tools, all of which were summarized in an excellent review by Levine and Rainesi n2 012.…”

Recent Progress in Fluorescence Imaging of the Near‐Infrared II Window

“…Imagingp lays ak ey role in the field of cancert herapy. [1] Fluorescenti maging, in particular,h as attracted considerable attention because of high sensitivity,h igh resolution, and simple operation, andt hus, has been widely utilized in the fields of biomedical andl ife science. Although magnetic resonance imaging( MRI), single-photon emission computed tomography (SPECT), and positrone mission tomography( PET) imaging technology have emerged, there are still great challenges in real-time, noninvasive, and high-resolutiont umor imaging in complex internal environments.…”