Quinone Derivatives Research Articles

Z-ligustilide: A review of its pharmacokinetics and pharmacology.

Z-ligustilide is a natural benzoquinone derivative found in many widely used Chinese herbal medicines such as Angelica sinensis (Oliv.) Diels as well as Ligusticum chuanxiong Hort and so on. It has been used as a part of traditional Chinese medicine and is also present in various Chinese medicine preparations. Pharmacokinetic studies have shown that Z-ligustilide has poor oral bioavailability in rats due to severe first-pass metabolic reactions. New evidence suggests that Z-ligustilide has a wide range of pharmacological properties, including anticancer, antiinflammatory, anti-oxidant as well as neuroprotective activities and so on. The literature discussed is derived from readily accessible papers spanning the early 1970s to the end of March 2019. Information were collected from journals, books, and online searches (Google Scholar, PubMed, Science Direct, Science Citation Index Finder, Springer link, and CNKI). This review intends to provide a comprehensive overview of the pharmacokinetics and pharmacology of Z-ligustilide in recent years, with a focus on its biological properties and mechanisms, which is of great significance for Chinese medicine.

FUNDAMENTAL AND APPLIED ASPECTS OF THE CHEMISTRY OF ACETYLENYLQUINONES

In addition to the reported synthetic routes for the acetylene derivatives of quinones, a detailed analysis of the fundamental chemical, physicochemical, and biological properties of this class of compounds is presented herein. The advantages of Pd- and Cu-catalyzed cross-coupling of terminal alkynes with iodarenes via the Sonogashira reaction to produce new acetylenylquinones with predetermined properties are examined. Here, combining quinoid and acetylene residues into one molecule gives the resulting compounds chemical specificity, as demonstrated by several reported examples of non-trivial transformations. In particular, the presence of the quinoid cycle significantly increases the electrophilicity of the triple bond and determines the range of transformation possibilities. Moreover, acetylenylquinones have heightened sensitivity to both external (such as the reaction temperature and the nature of the solvent) and internal (e.g., the structure of substituents in the nucleus and the acetylene fragment) factors. For example, regioselective cleavage of a strong triple bond under the action of amines is possible in the absence of a metal catalyst. Peri-substituted acetylenyl-9,10-anthraquinones are most suited for the synthetic route because of the proximity of the acetylene and carbonyl groups. Mechanisms of reactions of selective alkynylquinones are described.

FUNDAMENTAL AND APPLIED ASPECTS OF THE CHEMISTRY OF ACETYLENYLQUINONES

In addition to the reported synthetic routes for the acetylene derivatives of quinones, a detailed analysis of the fundamental chemical, physicochemical, and biological properties of this class of compounds is presented herein. The advantages of Pd- and Cu-catalyzed cross-coupling of terminal alkynes with iodarenes via the Sonogashira reaction to produce new acetylenylquinones with predetermined properties are examined. Here, combining quinoid and acetylene residues into one molecule gives the resulting compounds chemical specificity, as demonstrated by several reported examples of non-trivial transformations. In particular, the presence of the quinoid cycle significantly increases the electrophilicity of the triple bond and determines the range of transformation possibilities. Moreover, acetylenylquinones have heightened sensitivity to both external (such as the reaction temperature and the nature of the solvent) and internal (e.g., the structure of substituents in the nucleus and the acetylene fragment) factors. For example, regioselective cleavage of a strong triple bond under the action of amines is possible in the absence of a metal catalyst. Peri-substituted acetylenyl-9,10-anthraquinones are most suited for the synthetic route because of the proximity of the acetylene and carbonyl groups. Mechanisms of reactions of selective alkynylquinones are described.

Synthesis of enantiomerically pure oxygen-containing helical heterocycles via stereospecific rearrangement of benzofused-2,2′-diphenoquinone derivatives

Three different enantiomerically pure poly-condensed oxygen-containing heterocyclic compounds were synthesized by the rearrangement of enantiomerically pure (P)- and (M)-benzofused-2,2′-diphenoquinones. The three products were: a spiro compound bearing a γ-lactone ring, and two derivatives with a helical structure, one containing a δ-lactone ring and the other oxepin and furan rings. When the helical quinone derivative was heated in solution, the rearrangement proceeded with retention of configuration. Thus, (P)-quinone derivatives gave the corresponding (S)-spiro and (P)-helicene-like derivatives without compromising their enantiomeric purity, and vice versa.

Mapping the optoelectronic property space of small aromatic molecules

Small aromatic molecules and their quinone derivatives find use in organic transistors, solar-cells, thermoelectrics, batteries and photocatalysts. These applications exploit the optoelectronic properties of these molecules and the ease by which such properties can be tuned by the introduction of heteroatoms and/or the addition of functional groups. We perform a high-throughput virtual screening using the xTB family of density functional tight-binding methods to map the optoelectronic property space of ~250,000 molecules. The large volume of data generated allows for a broad understanding of how the presence of heteroatoms and functional groups affect the ionisation potential, electron affinity and optical gap values of these molecular semiconductors, and how the structural features – on their own or in combination with one another – allow access to particular regions of the optoelectronic property space. Finally, we identify the apparent boundaries of the optoelectronic property space for these molecules: regions of property space that appear off limits for any small aromatic molecule.

Benzoquinone derivatives with antioxidant activity inhibit activated hepatic stellate cells and attenuate liver fibrosis in TAA-induced mice

Liver fibrosis is a common pathological consequence of liver injury, which increases liver failure-related morbidity and mortality. Hence, anti-fibrotic treatment is urgently needed. Oxidative stress plays a pivotal role in the progression of liver fibrosis. Thus, targeting ROS may be an effective strategy for liver fibrosis treatment. In this study, we investigated four benzoquinones derivatives, including 5-isopropyl-2-methyl-1,4-benzoquinone (TQ), 2-tert-butyl-1,4-benzoquinone (tBu-Q) 2,5-dimethyl-p-benzoquinone (Dime-Q) and p-benzoquinone (Ph-Q), as well as the evaluation of their antioxidant activity and anti-fibrotic effects on activated hepatic stellate cells and TAA-induced mice. Electrochemical analysis showed that all compounds possessed antioxidant property. The result was first confirmed by in vitro experiments, which revealed potential anti-fibrotic activity of all four compounds at the cellular level. Benzoquinone derivatives act as ROS-scavenging molecules, which modulated the TLR4-CD14 signaling pathway to inhibit the expression of procaspase-1 and IL-1β in cells, induced apoptosis via a mitochondrial pathway by upregulating the ratio of Bax/Bcl-2 and by activating caspase-3, as well as inhibited the expression of the anti-apoptotic proteins FLIP and XIAP in activated LX-2 cells. In addition, a TAA (Thioacetamide)-induced mouse model was used to further validate the results. Treatment with benzoquinone derivatives significantly decreased the levels of liver injury markers and lipid peroxidation caused by excessive ROS, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA). Moreover, treatment with benzoquinone derivatives significantly inhibited extracellular matrix (ECM) deposition and downregulated the mRNA and protein expression of liver fibrosis markers, such as collagen I, alpha-smooth muscle actin (α-SMA), and TIMP-1. In summary, these results indicate that benzoquinone derivatives may act as potential therapeutic drugs against liver fibrosis.

Enzymatic Platforms for Sensitive Neurotransmitter Detection.

A convenient electrochemical sensing pathway was investigated for neurotransmitter detection based on newly synthesized silole derivatives and laccase/horseradish-peroxidase-modified platinum (Pt)/gold (Au) electrodes. The miniature neurotransmitter’s biosensors were designed and constructed via the immobilization of laccase in an electroactive layer of the Pt electrode coated with poly(2,6-bis(3,4-ethylenedioxythiophene)-4-methyl-4-octyl-dithienosilole) and laccase for serotonin (5-HT) detection, and a Au electrode modified with the electroconducting polymer poly(2,6-bis(selenophen-2-yl)-4-methyl-4-octyl-dithienosilole), along with horseradish peroxidase (HRP), for dopamine (DA) monitoring. These sensing arrangements utilized the catalytic oxidation of neurotransmitters to reactive quinone derivatives (the oxidation process was provided in the enzymes’ presence). Under the optimized conditions, the analytical performance demonstrated a convenient degree of sensitivity: 0.0369 and 0.0256 μA mM−1 cm−2, selectivity in a broad linear range (0.1–200) × 10−6 M) with detection limits of ≈48 and ≈73 nM (for the serotonin and dopamine biosensors, respectively). Moreover, the method was successfully applied for neurotransmitter determination in the presence of interfering compounds (ascorbic acid, L-cysteine, and uric acid).

Conformational Mobility Study in Mono Quinone Derivative of Calix[4]arene by Low Temperature NMR Spectroscopy

: Calix[4]monoquinone (3) has been synthesized by oxidation of rigid cone conformation of tripropoxy calix[4]arene (2), and conformational characteristics of this molecule have been studied by means of dynamic nuclear magnetic resonance (DNMR) and HH- correlated nuclear magnetic resonance spectroscopy (HH-COSY NMR). On the basis of the data that have been obtained, free Gibbs energy of activation (ΔG#) for quinone ring interconversion process of 3 was determined 12.3±0.05 Kcal/mol by coalescence approximation method.

Inclusion crystals of V-shaped host molecules having trialkoxybenzene moieties with a carborane or benzoquinone derivative

Crystallization of an o-carborane or benzoquinone derivative with adamantane-based molecules possessing pyrogallol derivatives resulted in the formation of inclusion crystals through CH⋯O or lone pair⋯π interactions.

Efficient electrochemical synthesis of robust, densely functionalized water soluble quinones

Conjugate addition of thiols to benzoquinones has been coupled to in situ electrochemical oxidation of the resulting hydroquinone to enable full substitution of quinone C-H bonds. The sulfonated thioether-substituted quinones exhibit high solublity and stability in aqueous solution and have redox potentials ranging from 440-750 mV vs. SHE. The electrosynthetic protocol is effective on >100 g scale.

Benzoquinone synthesis-related genes of Tribolium castaneum confer the robust antifungal host defense to the adult beetles through the inhibition of conidial germination on the body surface

Insects fight against invading microbial pathogens through various immune-related measures that comprise ‘internal’, ‘external’ as well as ‘social’ immunities. The defenses by external immunity associated with the cuticular integument are supposed to be of particular importance in repelling entomopathogenic fungi that infect host insects transcutaneously. Among such integument-related defenses, external secretions of benzoquinone derivatives typical of tenebrionid beetles have been suggested to play important roles in the antimicrobial defenses. In the present study, by utilizing the experimental infection system composed of the red flour beetle Tribolium castaneum and generalist ascomycete entomopathogens Beauveria bassiana and Metarhizium anisopliae, we performed the functional assays of the three T. castaneum genes whose involvement in benzoquinone synthesis in the adults has been reported, namely GT39, GT62 and GT63. Observations by scanning electron microcopy (SEM) revealed that the conidia of the two fungal species did not germinate on the wild-type adult body surface but did on the pupae. The expression analyses demonstrated that the levels of GT39 and GT62 mRNA increased from middle pupae and reached high in early adults while GT63 did not show a clear adult-biased expression pattern. The RNA interference-based knockdown of any of the three genes in pupae resulted in the adults compromised to the infection of the both fungal species. SEM observations revealed that the gene silencing allowed the conidial germination on the body surface of the knockdown beetles, thereby impairing the robust antifungal defense of adult beetles. Thus, we have provided direct experimental evidence for the functional importance in vivo of these benzoquinone synthesis-related genes that support the antifungal defense of tenebrionid beetles.

Application of quinone derivatives for spectrophotometric determination of drugs

The aim of this research is the development and validation of spectrophotometric methods for the determination of acetylcysteine and streptomycin sulfate, suitable for the standardization of test substances and analysis dosage forms.Materials and methods. The substances of the acetylcysteine and the streptomycin sulfate, the quinone derivatives (the solutions of sodium 1,2-naphthoquinone-4-sulfonate and 2,3-dichloro-1,4-naphthoquinone), as the analytical color reagents, were used for the experiment. The spectrophotometer Specord 200 for measuring the optical density was applied.Results. According to experimental data, the optimal conditions between the test substances and the added reagents were established. The factors affecting the character of the absorbance spectrum and the value of absorbance: the nature of the solution medium, the amount of added reagents, pH of the reaction mixture, conduction period of the reaction and reaction product resistance in time have been studied for the development of a methods of quantitative determination of acetylcysteine and streptomycin sulfate on based reactions with quinone derivatives.It was experimentally established that the sodium 1,2-naphthoquinone-4-sulfonate with streptomycin sulfate in the alkaline medium to form a colored composition with maximum light absorbance at 560 nm. The solution of 2,3-dichloro-1,4-naphthoquinone with acetylcysteine in the DMFA medium to form a colored composition with maximum light absorbance at 425 nm. It was necessary to heat it on the water bath for 10 min at 95 °С for more complete conduction period of reaction.According to SPU, the procedure of validation was determined. It has been proved that the developed techniques of the quantitative determination based on such characteristics as linearity, accuracy, validity, application range and robustness. The obedience to the Beer’s Law is 4.48–8.40 mg/100 ml for acetylcysteine and 2.00–8.00 mg/100 ml for streptomycin sulfate. Stoichiometric ratios of the reaction mixture component have been established by means of the method of isomolar series and continuous change method.Conclusion. As a result of this work, the optimal reaction conditions for the reaction of acetylcysteine with 2,3-dichloro-1,4-naphthoquinone and streptomycin sulfate with sodium 1,2-naphthoquinone-4-sulfonate have been established. Based on the obtained data, new spectrophotometric methods for the quantitative determination of the investigated drugs were developed and tested on the dosage forms. It is proved that the developed methods are simple, reproducible and expressive.

Discovery of nitrogenous sesquiterpene quinone derivatives from sponge Dysidea septosa with anti-inflammatory activity in vivo zebrafish model.

Two unique nitrogenous sesquiterpene quinone meroterpenoids, dysidinoid B (1) and dysicigyhone A (2), together with eight known analogues (3-10) were isolated and characterized from the marine sponge Dysidea septosa. Their structures with absolute configurations were established by a combination of extensive spectroscopic, electron circular dichroism (ECD) and single-crystal X-ray diffraction data analysis. Structurally, dysicigyhone A (2) possessed a unique benzo[d]oxazolidine-2-one unit. Additionally, dysidinoid B (1) exhibited significant anti-inflammatory effect by inhibiting TNF-α and IL-6 generation with IC50 values of 9.15μM and 17.62μM, respectively. Further in vivo anti-inflammatory assay verified that the dysidinoid B (1) alleviated the CuSO4-induced robust acute inflammatory response in zebrafish model.

New aryloxy-quinone derivatives with promising activity on Trypanosoma cruzi.

Continuing with a program to develop new quinone derivatives as biologically active compounds, we designed and synthesized a new series of aryloxy-quinones, which were evaluated in vitro against Trypanosoma cruzi in epimastigote form. Chemical modifications in three specific moieties on the aryloxy-quinone core were considered for developing new anti-T. cruzi agents. The majority of our new quinones showed higher potency (IC50 values of <0.70 µM) than nifurtimox, a known pharmaceutical used as a baseline drug (IC50 values of 7.00 µM); however, only two of them elicited higher selectivity than nifurtimox against Vero cells. A structure-activity relationship analysis provided information about the stereoelectronic features of these compounds, which are responsible for an increase in trypanosomicidal activity. Using a pharmacophore model, we mapped the substitution patterns of the five pharmacophoric features of trypanosomicidal activity. We chose the Epc1 compounds and found no relationship with the trypanosomicidal effects. These results provided useful information about the structural characteristics for developing new aryloxy-quinones with higher potency against the protozoan parasite T. cruzi.

Bismuth-catalyzed methylation and alkylation of quinone derivatives with tert-butyl peroxybenzoate as an oxidant

A bismuth-catalyzed methylation of quinones in the presence of tert-butyl peroxybenzoate (TBPB) was developed via a radical reaction mechanism. Particularly, TBPB was used not only as an efficient oxidant, but also as a green methyl source in such transformation. Moreover, this method could also be efficiently extended to the alkylation of quinones. This reaction tolerated a series of functional groups and prepared a series of derivatives of vitamin K3 and benzoquinone. Notably, antimalarial parvaquone was synthesized by the reaction.

Embelin as a Novel Inhibitor of PKC in the Prevention of Platelet Activation and Thrombus Formation.

Embelin is a quinone derivative and found in the fruits of Embelia ribes Burm.f. Embelin has been identified as a small molecular inhibitor of X-chromosome-linked inhibitor of apoptosis proteins, and has multiple biological activities, including antioxidation, anti-inflammation, and antitumor effects. However, the effect of embelin in platelets remains unclear. Thus, this study investigated the antiplatelet mechanism of embelin. Our data revealed that embelin could inhibit platelet aggregation induced by various agonists, including the protein kinase C (PKC) activator phorbol 12,13-dibutyrate (PDBu). Embelin, as well as the PKC inhibitor Ro 31-8220, markedly reduced PDBu-mediated phosphorylation of the PKC substrate, suggesting that embelin may be a PKC inhibitor for platelets. Embelin could block PKC downstream signaling and events, including the inhibition of protein kinase B and mitogen-activated protein kinase activation, granule release, and glycoprotein IIbIIIa activation. Moreover, embelin could delay thrombus formation in the mesenteric microvessels of mice, but did not significantly affect the tail bleeding time. In conclusion, we demonstrated that embelin is a PKC inhibitor and possesses antiplatelet and antithrombotic effects. The further analysis is necessary to more accurately determine clinical therapeutic potential of embelin in all clinical thromboembolic events with disturbance of thrombocyte function.

The antidiabetic effect of thymoquinone: A systematic review and meta-analysis of animal studies.

Thymoquinone (2-isopropyl-5-methylbenzo-1, 4-quinone) (TQ) is a quinone derivative with a yellow crystalline appearance, abundantly found in black cumin, Nigella sativa L. TQ has diverse pharmacological properties. The aim of this systematic review on the antidiabetic effects of TQ is to evaluate the currently available evidence and conduct meta-analysis. A literature search of articles published until 25 January 2019 was done on PubMed, EMBASE, Web of Sciences and Scopus databases, using relevant keywords. The meta-analysis included 18 studies that examined the serum glucose (SG) level or serum insulin level or body weight (BW). In the meta-analysis it was found that with an overall pooled standardized mean difference (SMD) of -9.176 mg/dl (95%CI: -10.759, -7.593; p = 0.000); TQ reduced the SG level (-9.176 mg/dl) significantly in the STZ-induced diabetes model. Moreover, a meta-analysis of the effect of TQ on BW demonstrated that TQ has a statistically significant effect on the BW of diabetic animals with an overall pooled SMD of 4.509 (95%CI: 3.234, 5.784; p = 0.000). In addition, the overall pooled estimate of the level of serum insulin was significant with SMD of 1.681 (95%CI: 0.858, 2.503; p = 0.000). Therefore, the meta-analysis showed that TQ has a significant antidiabetic effect through its action on the SG, serum insulin level, and BW of the animals.

564 Melasolv, a skin lightening compound with different mechanisms to regulate skin pigmentation

The pigmentation of human skin (nevi, senile lentigines, melasma, etc) is regulated by a complex process involving the synthesis and distribution of melanin. Overexpression of melanin is induced by the off-balance between the signals which regulates melanin synthesis, this can be caused due to a response to external or internal stimulus that often affects the genes related to melanogenesis. To date, many studies have focused on developing direct enzymatic inhibitors of tyrosinase in order to achieve a skin-lightening effect. However, it was also reported that these direct inhibitors could be converted to quinone derivatives by tyrosinase-catalyzed oxidation, which lead to undesirable outcomes. Therefore, we have studied intrinsic inhibitory factors of melanogenesis in skin with the objective to achieve a lightening effect without the undesirable potential side effects. It was reported that non-coding RNAs including H19, miR125b and WIF1 were decreased in hyper-pigmented skin such as melasma and nevi. And it was found out that melanogenesis could be inhibited by increasing these lightening genes expression in normal human epidermal melanocytes and keratinocytes. Our group showed that the 3, 4, 5-trimethoxy cinnamate thymol ester (TCTE, Melasolv®), synthesized from gallic acid, is a lightening active which decreases tyrosinase protein formation by regulating the MITF. Likewise, we have also observed that Melasolv significantly decreased melanogenesis by increasing expression of the lightening genes H19, miR125b and WIF1 in the skin cells. Finally, we have confirmed the lightening effect of Melasolv in 3D human skin equivalent. Nonetheless, since Melasolv is not a direct inhibitor of tyrosinase enzymatic activity, it is extremely unlikely that nocive quinone derivatives conversions occur. From these results, we have proposed Melasolv as an active for lightening effects with a safer profile, when considering undesirable effects, to treat pigmentary disorder and uneven skin color.

Symmetric All-Quinone Aqueous Battery

Lithium-ion batteries continue to dominate portable electronics and electric vehicles markets for its high energy density/specific energy.1However, combustible electrolytes and expensive cathodes pose safety and cost concerns to consumers.2 Further cost reduction is expected to be limited after decades of development.3Next generation energy storage devices call for safe, cheap, resource-abundant and flexible batteries.2, 4 Rechargeable batteries with cost-effective redox active materials and aqueous electrolytes can potentially meet these requirements.5 Aqueous battery chemistries include lead-acid batteries, nickel-metal hydride aqueous batteries, and emerging aqueous lithium/sodium-ion batteries, but they all have their Achilles’ heels.6 - 12 Here we report a symmetric all-quinone aqueous battery based entirely on Earth-abundant elements that uses a naturally-occurring dye as the redox-active material in both positive and negative electrodes. We demonstrate a symmetric all-quinone cell with 1.04 V of open circuit voltage, 163 mAh/g of capacity, and 100 cycles at 10C with 100% of depth of discharge. The use of the same quinone in a symmetric setup expands the repertoire of inexpensive redox active materials for aqueous rechargeable batteries, and the simple cell design will enable optimizations toward safe, cheap, lightweight, and flexible electronics in the future. Natural abundance and cheap commercial source promise its low cost when produced at large scale. In addition, we demonstrate that other fused quinone derivatives can also be used for symmetric quinone-acid batteries. Further optimization of fused quinones with improved reduction potential and stability, and cell engineering of electrode composition and morphology can further improve the performance of the battery. References Zubi, G.; Dufo-López, R.; Carvalho, M.; Pasaoglu, G., The lithium-ion battery: State of the art and future perspectives. Renewable and Sustainable Energy Reviews 2018, 89, 292-308. Armand, M.; Tarascon, J. M., Building better batteries. Nature 2008, 451, 6. Hsieh, I.-Y. L.; Pan, M. S.; Chiang,Y.-M.; and Green, W. H. Learning only buys you so much: practical limits on battery price reduction Applied Energy 2019, 239, 218. Larcher, D.; Tarascon, J. M., Towards greener and more sustainable batteries for electrical energy storage. Nat. Chem. 2015, 7(1), 19-29. Beck, F.; Rüetschi, P., Rechargeable batteries with aqueous electrolytes. Electrochimica Acta 2000, 45, 16. Chen, H. Y.; Li, A. J.; Finlow, D. E., The lead and lead-acid battery industries during 2002 and 2007 in China. Journal of Power Sources 2009, 191(1), 22-27. van der Kuijp, T.; Huang, L.; Cherry, C. R., Health hazards of China's lead-acid battery industry: a review of its market drivers, production processes, and health impacts. Environmental Health 2013, 12(61), 10. Ruetschi, P., Aging mechanisms and service life of lead–acid batteries. Journal of Power Sources 2004, 127(1-2), 33-44. Zou, X., Kang, Zongxuan, Shu, Dong, Liao, Yuqing, Gong, Yibin, He, Chun, Hao, Junnan, Zhong, Yayun, Effects of carbon additives on the performance of negative electrode of lead-carbon battery. Electrochimica Acta 2015, 151, 89-98. Rodrigues, L. E. O. C.; Mansur, M. B., Hydrometallurgical separation of rare earth elements, cobalt and nickel from spent nickel–metal–hydride batteries. Journal of Power Sources 2010, 195(11), 3735-3741. Ying, T. K.; Gao, X. P.; Hu, W. K.; Wu, F.; Noréus, D., Studies on rechargeable NiMH batteries. Int. J. Hydrogen Energy 2006, 31(4), 525-530. Kim, H.; Hong, J.; Park, K. Y.; Kim, H.; Kim, S. W.; Kang, K., Aqueous rechargeable Li and Na ion batteries. Chem. Rev. 2014, 114(23), 11788-827. Figure 1

A Quencher‐Fluorophore‐Type Probe for Detection and Imaging of NADPH in Human Breast Cancer Cells

A new fluorogenic trimethyl lock quinone (TLQ) derivative, designated as the quencher‐TLQ‐fluorophore‐type probe (Q‐TLQ‐F), was developed for selective detection of nicotinamide adenine dinucleotide phosphate (NADPH). By taking advantage of the well‐known facile intramolecular ring cyclization reaction (δ‐lactonization) of TLQ that can release a reporter molecule upon reduction, Q‐TLQ‐F was successfully applied for the detection of physiological NADPH generated by glucose‐6‐phosphate dehydrogenase in human breast cancer MDA‐MB‐231 cells.