Submit to Molecules Review for Molecules Propose a Special Issue

Journal Browser

► Journal Browser

Fluorescent Probes as Powerful Tools in Medicinal Chemistry

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 13121

Share This Special Issue

Special Issue Editor

Prof. Dr. Peter Verwilst

E-Mail Website
Guest Editor

Rega Institute for Medical Research, KU Leuven, Leuven, Belgium
Interests: medicinal chemistry; fluorescent probes; antimicrobial drug design; GPCR drug design; neurodegenerative diseases

Special Issue Information

Dear Colleagues,

Fluorescent tools play a major role in many aspects of the drug discovery and design process and have become ubiquitous. Applications include fluorescent assay development for (high throughput) screening, the design of reactive tools to guide the design of (covalent) inhibitors, designing and discovering imaging tools for biomarkers, imaging drug targets in small animal models, etc.

The aim of this Special Issue is to highlight the role of these “workhorses” in chemical biology and medicinal chemistry and publish recent advancements of fluorescent tools used in the context of, or potentially applied to, drug and imaging agent development. The submission of both research reports and critical reviews, covering fluorescent probes in medicinal chemistry in the broadest sense, to this Special Issue is highly encouraged

Prof. Dr. Peter Verwilst
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

fluorescent probe design
drug discovery and development
fluorescent assays
bioimaging tools
medicinal chemistry

Published Papers (5 papers)

Download All Papers

Research

Jump to: Review

20 pages, 3110 KiB

Open AccessArticle

Sensitive Assay for the Lactonase Activity of Serum Paraoxonase 1 (PON1) by Harnessing the Fluorescence Turn-On Characteristics of Bioorthogonally Synthesized and Geometrically Controlled Chemical Probes

by Bo-Kai Fang, Chia-Yen Dai, Scott Severance, Chi-Ching Hwang, Chien-Hui Huang, Sin-Yu Hou, Bao-Lin Yeh, Ming-Mao Gong, Yun-Hao Chou, Jeh-Jeng Wang and Tzu-Pin Wang

Molecules 2022, 27(8), 2435; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27082435 - 09 Apr 2022

Cited by 1 | Viewed by 2433

Abstract

The lactonase activity of paraoxonase 1 (PON1) has a crucial antiatherogenic function, and also serves as an important biochemical marker in human blood because the aberrant lactonase activity of PON1 is a key indicator for a number of diverse human diseases. However, no sensitive fluorescence assays that detect PON1 lactonase activity are available. We report the synthesis of two fluorescence turn-on chemical probes 16a and 16b (16) able to quantify PON1 lactonase activity. The chemical probes were constructed utilizing a disulfide-containing bicyclononyne, derivatives of rhodamine B and carboxyfluorescein, and reactions including copper-free azide–alkyne cycloaddition. Fluorescence quenching in 16 was characterized by spectroscopic studies and was mainly attributed to the effect of contact quenching. Kinetic analysis of 16b confirmed the outstanding reactivity and specificity of 16b with thiols in the presence of general base catalysts. The 16b-based assay was employed to determine PON1 lactonase activity, with a linear range of 10.8–232.1 U L⁻¹ and detection limit (LOD) of 10.8 U L⁻¹, to quantify serum PON1 activity in human sera, and to determine the K_i of 20.9 μM for the 2-hydroxyquinoline inhibition of PON1 lactonase. We are employing 16b to develop high-throughput assays for PON1 lactonase activity. Full article

(This article belongs to the Special Issue Fluorescent Probes as Powerful Tools in Medicinal Chemistry)

► Show Figures

Graphical abstract

11 pages, 3814 KiB

Open AccessArticle

High-Affinity Ratiometric Fluorescence Probe Based on 6-Amino-2,2′-Bipyridine Scaffold for Endogenous Zn²⁺ and Its Application to Living Cells

by Masayori Hagimori, Fumiko Hara, Naoko Mizuyama, Takeshi Fujino, Hideo Saji and Takahiro Mukai

Molecules 2022, 27(4), 1287; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27041287 - 14 Feb 2022

Cited by 5 | Viewed by 1846

Abstract

Zinc is an essential trace element involved in many biological activities; however, its functions are not fully understood. To elucidate the role of endogenous labile Zn²⁺, we developed a novel ratiometric fluorescence probe, 5-(4-methoxyphenyl)-4-(methylsulfanyl)-[2,2′-bipyridin]-6-amine (6 (rBpyZ)) based on the 6-amino-2,2′-bipyridine scaffold, which acts as both the chelating agent for Zn²⁺ and the fluorescent moiety. The methoxy group acted as an electron donor, enabling the intramolecular charge transfer state of 6 (rBpyZ), and a ratiometric fluorescence response consisting of a decrease at the emission wavelength of 438 nm and a corresponding increase at the emission wavelength of 465 nm was observed. The ratiometric probe 6 (rBpyZ) exhibited a nanomolar-level dissociation constant (K_d = 0.77 nM), a large Stokes shift (139 nm), and an excellent detection limit (0.10 nM) under physiological conditions. Moreover, fluorescence imaging using A549 human lung adenocarcinoma cells revealed that 6 (rBpyZ) had good cell membrane permeability and could clearly visualize endogenous labile Zn²⁺. These results suggest that the ratiometric fluorescence probe 6 (rBpyZ) has considerable potential as a valuable tool for understanding the role of Zn²⁺ in living systems. Full article

(This article belongs to the Special Issue Fluorescent Probes as Powerful Tools in Medicinal Chemistry)

► Show Figures

Figure 1

14 pages, 4933 KiB

Open AccessArticle

Novel Boronate Probe Based on 3-Benzothiazol-2-yl-7-hydroxy-chromen-2-one for the Detection of Peroxynitrite and Hypochlorite

by Julia Modrzejewska, Marcin Szala, Aleksandra Grzelakowska, Małgorzata Zakłos-Szyda, Jacek Zielonka and Radosław Podsiadły

Molecules 2021, 26(19), 5940; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26195940 - 30 Sep 2021

Cited by 8 | Viewed by 2034

Abstract

Derivatives of coumarin, containing oxidant-sensitive boronate group, were recently developed for fluorescent detection of inflammatory oxidants. Here, we report the synthesis and the characterization of 3-(2-benzothiazolyl)-7-coumarin boronic acid pinacol ester (BC-BE) as a fluorescent probe for the detection of peroxynitrite (ONOO^–), with high stability and a fast response time. The BC-BE probe hydrolyzes in phosphate buffer to 3-(2-benzothiazolyl)-7-coumarin boronic acid (BC-BA) which is stable in the solution even after a prolonged incubation time (24 h). BC-BA is slowly oxidized by H₂O₂ to form the phenolic product, 3-benzothiazol-2-yl-7-hydroxy-chromen-2-one (BC-OH). On the other hand, the BC-BA probe reacts rapidly with ONOO⁻. The ability of the BC-BA probe to detect ONOO^– was measured using both authentic ONOO^– and the system co-generating steady-state fluxes of O₂^•^– and ^•NO. BC-BA is oxidized by ONOO^– to BC-OH. However, in this reaction 3-benzothiazol-2-yl-chromen-2-one (BC-H) is formed in the minor pathway, as a peroxynitrite-specific product. BC-OH is also formed in the reaction of BC-BA with HOCl, and subsequent reaction of BC-OH with HOCl leads to the formation of a chlorinated phenolic product, which could be used as a specific product for HOCl. We conclude that BC-BA shows potential as an improved fluorescent probe for the detection of peroxynitrite and hypochlorite in biological settings. Complementation of the fluorescence measurements by HPLC-based identification of oxidant-specific products will help to identify the oxidants detected. Full article

(This article belongs to the Special Issue Fluorescent Probes as Powerful Tools in Medicinal Chemistry)

► Show Figures

Figure 1

15 pages, 2847 KiB

Open AccessCommunication

Flavylium-Based Hypoxia-Responsive Probe for Cancer Cell Imaging

by Thitima Pewklang, Sirawit Wet-osot, Sirilak Wangngae, Utumporn Ngivprom, Kantapat Chansaenpak, Chuthamat Duangkamol, Rung-Yi Lai, Parinya Noisa, Mongkol Sukwattanasinitt and Anyanee Kamkaew

Molecules 2021, 26(16), 4938; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26164938 - 15 Aug 2021

Cited by 6 | Viewed by 3143

Abstract

A hypoxia-responsive probe based on a flavylium dye containing an azo group (AZO-Flav) was synthesized to detect hypoxic conditions via a reductase-catalyzed reaction in cancer cells. In in vitro enzymatic investigation, the azo group of AZO-Flav was reduced by a reductase in the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH) followed by fragmentation to generate a fluorescent molecule, Flav-NH₂. The response of AZO-Flav to the reductase was as fast as 2 min with a limit of detection (LOD) of 0.4 μM. Moreover, AZO-Flav displayed high enzyme specificity even in the presence of high concentrations of biological interferences, such as reducing agents and biothiols. Therefore, AZO-Flav was tested to detect hypoxic and normoxic environments in cancer cells (HepG2). Compared to the normal condition, the fluorescence intensity in hypoxic conditions increased about 10-fold after 15 min. Prolonged incubation showed a 26-fold higher fluorescent intensity after 60 min. In addition, the fluorescence signal under hypoxia can be suppressed by an electron transport process inhibitor, diphenyliodonium chloride (DPIC), suggesting that reductases take part in the azo group reduction of AZO-Flav in a hypoxic environment. Therefore, this probe showed great potential application toward in vivo hypoxia detection. Full article

(This article belongs to the Special Issue Fluorescent Probes as Powerful Tools in Medicinal Chemistry)

► Show Figures

Graphical abstract

Review

Jump to: Research

19 pages, 2199 KiB

Open AccessReview

Curcumin Scaffold as a Multifunctional Tool for Alzheimer’s Disease Research

by Haijun Yang, Fantian Zeng, Yunchun Luo, Chao Zheng, Chongzhao Ran and Jian Yang

Molecules 2022, 27(12), 3879; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27123879 - 17 Jun 2022

Cited by 13 | Viewed by 2966

Abstract

Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders, which is caused by multi-factors and characterized by two histopathological hallmarks: amyloid-β (Aβ) plaques and neurofibrillary tangles of Tau proteins. Thus, researchers have been devoting tremendous efforts to developing and designing new molecules for the early diagnosis of AD and curative purposes. Curcumin and its scaffold have fluorescent and photochemical properties. Mounting evidence showed that curcumin scaffold had neuroprotective effects on AD such as anti-amyloidogenic, anti-inflammatory, anti-oxidative and metal chelating. In this review, we summarized different curcumin derivatives and analyzed the in vitro and in vivo results in order to exhibit the applications in AD diagnosis, therapeutic monitoring and therapy. The analysis results showed that, although curcumin and its analogues have some disadvantages such as short wavelength and low bioavailability, these shortcomings can be conquered by modifying the structures. Curcumin scaffold still has the potential to be a multifunctional tool for AD research, including AD diagnosis and therapy. Full article

(This article belongs to the Special Issue Fluorescent Probes as Powerful Tools in Medicinal Chemistry)

► Show Figures