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Accumulation of acylcarnitines is a characteristic feature of various metabolic disorders affecting fatty acid metabolism. Despite extensive research, no specific molecules have been identified to induce ferroptosis through the regulation of acylcarnitine metabolism. In this study, acylcarnitine accumulation was identified based on cell metabolomics study after the treatment with Stemona alkaloid derivative (SA-11), which was proved to induce ferroptosis in our previous research. Furthermore, the CPT-1 level was proved to significantly increase, while the CPT-2 level indicated no significant difference, which resulted in the accumulation of acylcarnitine. Besides, the ferroptosis-inducing ability of SA-11 was significantly enhanced by the addition of exogenous acylcarnitine, presumably due to the production of additional ROS. This hypothesis was corroborated by the observation of increased ROS levels in HCT-116 cells treated with SA-11 compared to the control group. These findings suggest that targeting acylcarnitine metabolism, particularly through CPT-1, may offer a novel therapeutic strategy for cancer treatment by enhancing ferroptosis induction. [ABSTRACT FROM AUTHOR]

Accumulation of acylcarnitines is a characteristic feature of various metabolic disorders affecting fatty acid metabolism. Despite extensive research, no specific molecules have been identified to induce ferroptosis through the regulation of acylcarnitine metabolism. In this study, acylcarnitine accumulation was identified based on cell metabolomics study after the treatment with Stemona alkaloid derivative (SA-11), which was proved to induce ferroptosis in our previous research. Furthermore, the CPT-1 level was proved to significantly increase, while the CPT-2 level indicated no significant difference, which resulted in the accumulation of acylcarnitine. Besides, the ferroptosis-inducing ability of SA-11 was significantly enhanced by the addition of exogenous acylcarnitine, presumably due to the production of additional ROS. This hypothesis was corroborated by the observation of increased ROS levels in HCT-116 cells treated with SA-11 compared to the control group. These findings suggest that targeting acylcarnitine metabolism, particularly through CPT-1, may offer a novel therapeutic strategy for cancer treatment by enhancing ferroptosis induction. [ABSTRACT FROM AUTHOR]

Accumulation of acylcarnitines is a characteristic feature of various metabolic disorders affecting fatty acid metabolism. Despite extensive research, no specific molecules have been identified to induce ferroptosis through the regulation of acylcarnitine metabolism. In this study, acylcarnitine accumulation was identified based on cell metabolomics study after the treatment with Stemona alkaloid derivative (SA-11), which was proved to induce ferroptosis in our previous research. Furthermore, the CPT-1 level was proved to significantly increase, while the CPT-2 level indicated no significant difference, which resulted in the accumulation of acylcarnitine. Besides, the ferroptosis-inducing ability of SA-11 was significantly enhanced by the addition of exogenous acylcarnitine, presumably due to the production of additional ROS. This hypothesis was corroborated by the observation of increased ROS levels in HCT-116 cells treated with SA-11 compared to the control group. These findings suggest that targeting acylcarnitine metabolism, particularly through CPT-1, may offer a novel therapeutic strategy for cancer treatment by enhancing ferroptosis induction. [ABSTRACT FROM AUTHOR]

NAD(P)H is crucial for biosynthetic reactions and antioxidant functions. However, the current probes developed for detecting NAD(P)H in vivo require intratumoral injection, which limited their application for animal imaging. To address this issue, we have developed a liposoluble cationic probe, KC8, which exhibits excellent tumor‐targeting ability and near‐infrared (NIR) fluorescence after reaction with NAD(P)H. By using KC8, it was demonstrated for the first time that the level of NAD(P)H in the mitochondria of living colorectal cancer (CRC) cells was highly related to the abnormality of the p53. Furthermore, KC8 was successfully used to differentiate not only between tumor and normal tissue but also between tumors with p53 abnormality and normal tumors when administered intravenously. Finally, we evaluated tumor heterogeneity through two fluorescent channels after treating a tumor with 5‐Fu. This study provides a new tool for real‐time monitoring of the p53 abnormality of CRC cells. [ABSTRACT FROM AUTHOR]

NAD(P)H is crucial for biosynthetic reactions and antioxidant functions. However, the current probes developed for detecting NAD(P)H in vivo require intratumoral injection, which limited their application for animal imaging. To address this issue, we have developed a liposoluble cationic probe, KC8, which exhibits excellent tumor‐targeting ability and near‐infrared (NIR) fluorescence after reaction with NAD(P)H. By using KC8, it was demonstrated for the first time that the level of NAD(P)H in the mitochondria of living colorectal cancer (CRC) cells was highly related to the abnormality of the p53. Furthermore, KC8 was successfully used to differentiate not only between tumor and normal tissue but also between tumors with p53 abnormality and normal tumors when administered intravenously. Finally, we evaluated tumor heterogeneity through two fluorescent channels after treating a tumor with 5‐Fu. This study provides a new tool for real‐time monitoring of the p53 abnormality of CRC cells. [ABSTRACT FROM AUTHOR]

A cysteine-specific fluorescent probe with a wide concentration detection range was used to monitor changes in cysteine levels in HeLa cells under stress and to demarcate the boundary of a xenograft tumour. [ABSTRACT FROM AUTHOR]

We report herein a caged luciferin probe Cy-Hy as a sequentially activated probe to selectively and sensitively sense L -Cys and H2O2. The probe displayed fluorescence and bioluminescence responses toward the two analytes. Utilizing the present probe, cellular excess L -Cys-induced H2O2 up-regulation was observed for the first time in living MDA-MB-231 cells. [ABSTRACT FROM AUTHOR]

Organisms are operating and evolving with a highly sophisticated and intelligent defense mechanism to resist bacterial and viral infections. This process involves a variety of reactive oxygen species (ROS), and they coordinate with each other to support different physiological activities. Due to its strong oxidizing properties, hypochlorous acid (HClO), a part of ROS, is a powerful antimicrobial agent in living organisms and exerts a crucial role in the immune system. However, the excessive production of HClO can cause cell damage and even cell death. Herein, we combined benzene-conjugated benzopyrylium as the fluorophore and dimethylthiocarbamoyl chloride as the recognition site to rationally design a probe (BBD). The fluorescence of the probe was quenched based on an effective PET molecular mechanism. Surprisingly, BBD exhibited a turn-on red fluorescence signal for HClO with ultra-fast response (5 s) and high selectivity. Moreover, BBD located mitochondria well and it was found that the abundance of HClO is higher in HeLa cells compared to that in normal cells. Finally, BBD was successfully applied to the visualization of HClO in zebrafish and nude mice. [ABSTRACT FROM AUTHOR]

Cyanide ions (CN−) are widely used in chemical and industrial processes, but not only can they cause environmental pollution, what is worse is that when a small amount of cyanide enters the human body, in the less severe cases, they pose health risks, and in the more severe cases, they can lead to death. The development of a practical cyanide probe is extremely urgent. In this work, with α,β-unsaturated ketones conjugated with ethylenediamine coumarin as a fluorophore and reaction site, boron fluoride was introduced to adjust the ICT and reactivity to construct a ratiometric fluorescent probe for the highly sensitive detection of CN−. The process was rapid within 40 s and can be monitored by the naked eye. The probe demonstrated a low detection limit (0.072 μM). Furthermore, the probe was used to detect CN− in the test strip, soil, and water. In addition, cell imaging experiments indicated the probe can be used in biological determination of cyanide poisoning. [ABSTRACT FROM AUTHOR]

Despite the unprecedented development of SO2 fluorescent probes in the past five years, the water-solubility of these probes is still an important factor related to their practical application. In previous work, we have studied SO2 detection by coupling quinoline and coumarin. Although the water solubility of the probe was improved, SO2 detection in a 100% aqueous medium was not fully achieved. Therefore, based on the previous system, we conjugated two quinolines to realize a 100% water-soluble sulfur dioxide fluorescent probe. The Probe showed a large Stokes shift (170 nm). Besides, the Probe could respond to SO2 within 1.5 min with high selectivity and sensitivity (LOD = 0.29 μM). In addition, fluorescence co-localization studies suggested that the Probe could be used for monitoring SO2 in the mitochondria of HeLa cells and living mice. It is believed that such an excellent probe will have a wide application prospect in the future. [ABSTRACT FROM AUTHOR]

We report herein a strategy involving using a single fluorescent probe with the assistance of two pH conditions to simultaneously detect cysteine and homocysteine quantitatively. The concentrations of Cys and Hcy in human serum samples were found to display a positive correlation, which might promote a further understanding of thiol-related diseases. [ABSTRACT FROM AUTHOR]

Covering: 2000–2018 In this review, we highlight recent examples of natural product total syntheses employing transition metal-mediated/catalyzed carbonylative cyclization strategies to build key ring systems. It mainly covers carbonylative cyclizations for the construction of O-heterocycles, N-heterocycles and carbocycles including cyclic ketones and phenols. The reaction types include carbonylation of epoxide to β-lactones, carbonylative (macro)lactonization/lactamization, the Semmelhack reaction, tandem hydroformylation–cyclization, the Pauson–Khand reaction, carbonylative C–H activation cyclization, the Stille/Suzuki carbonylation, [n + m + 1] carbonylative cycloaddition, the Dötz annulation, and others. [ABSTRACT FROM AUTHOR]

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The first total syntheses of the stemona alkaloids bisdehydroneostemoninine and bisdehydrostemoninine in racemic forms have been achieved. The synthetic strategy features a novel palladium‐catalyzed carbonylative spirolactonization of a hydroxycyclopropanol to rapidly construct the oxaspirolactone moiety. It also features a Lewis acid promoted tandem Friedel–Crafts cyclization and lactonization to form the 5‐7‐5 tricyclic core of the target stemona alkaloids. Core strength: The first total syntheses of the stemona alkaloids bisdehydroneostemoninine and bisdehydrostemoninine are reported. The synthesis features a novel palladium‐catalyzed carbonylative spirolactonization to rapidly construct the oxaspirolactone moiety and a Lewis acid promoted tandem Friedel–Crafts cyclization and lactonization to form the 5‐7‐5 tricyclic core of the target alkaloids. [ABSTRACT FROM AUTHOR]

A series of amide anthraquinone derivatives, an important component of some traditional Chinese medicines, were structurally modified and the resulting antitumor activities were evaluated. The compounds showed potent anti-proliferative activities against eight human cancer cell lines, with no noticeable cytotoxicity towards normal cells. Among the candidate compounds, 1-nitro-2-acyl anthraquinone-leucine (8a) showed the greatest inhibition of HCT116 cell activity with an IC50 of 17.80 μg/mL. In addition, a correlation model was established in a three-dimensional quantitative structure-activity relationship (3D-QSAR) study using Comparative Molecular Field Analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). Moreover, compound 8a effectively killed tumor cells by reactive oxygen species (ROS)-JNK activation, causing an increase in ROS levels, JNK phosphorylation, and mitochondrial stress. Cytochrome c was then released into cytoplasm, which, in turn activated the cysteine protease pathway and ultimately induced tumor cell apoptosis, suggesting a potential use of this compound for colon cancer treatment. [ABSTRACT FROM AUTHOR]