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WO2025112010A1 - Régulateur d'autophagie, son procédé de préparation et son utilisation - Google Patents

Régulateur d'autophagie, son procédé de préparation et son utilisation Download PDF

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Publication number
WO2025112010A1
WO2025112010A1 PCT/CN2023/135725 CN2023135725W WO2025112010A1 WO 2025112010 A1 WO2025112010 A1 WO 2025112010A1 CN 2023135725 W CN2023135725 W CN 2023135725W WO 2025112010 A1 WO2025112010 A1 WO 2025112010A1
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group
autophagy
alkyl
cell
autophagy regulator
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PCT/CN2023/135725
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English (en)
Chinese (zh)
Inventor
宋国芬
王怀雨
李鹏辉
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Shenzhen Institute of Advanced Technology of CAS
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Shenzhen Institute of Advanced Technology of CAS
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Priority to PCT/CN2023/135725 priority Critical patent/WO2025112010A1/fr
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence

Definitions

  • the present invention relates to the field of probes, and in particular to an autophagy regulator and a preparation method and application thereof.
  • Autophagy is the self-digestion of lysosomes or vacuoles and the degradation and recycling of cell contents, which is essential for maintaining homeostasis and energy balance in cells. At the same time, it has a wide range of biological effects, including organelle remodeling, protein and organelle quality control, tumor suppression, pathogen elimination, immune and inflammatory regulation, and cell survival. Studies have shown that dysfunction in the autophagy process is related to a variety of diseases, including cancer, neurodegenerative diseases, diabetes, autoimmune diseases, and cardiovascular diseases. Therefore, autophagy regulation is of great significance for the treatment of a variety of diseases. At present, targeted drugs for autophagy in various diseases are also under further development.
  • the existing autophagy regulators include rapamycin, chloroquine, etc., which can only activate or inhibit autophagy, and do not produce fluorescence after binding to the target, so fluorescence observation is not possible. Especially when used for tumor treatment, the efficacy and tumor selectivity need to be improved.
  • the present invention aims to solve at least one of the technical problems existing in the prior art.
  • the present invention proposes a dual-targeted fluorescent organic small molecule autophagy activator and autophagy inhibitor and its application, aiming to solve the problem that the prior art has a single autophagy regulation target and no cell selectivity, and poor cancer cell killing efficacy.
  • the autophagy regulator is a compound having a structure as shown in formula (I), or a pharmaceutically acceptable salt thereof:
  • the R1 is selected from any one of hydrogen and C1-C4 alkyl; the R2 is selected from any one of hydrogen and C1-C4 alkyl; the R3 is selected from any one of hydrogen, C1-C4 alkyl, and C1-C4 alkoxy; and the X is selected from any one of halogen atom, BF4 , and ClO4 .
  • the autophagy regulator is an autophagy activator and an autophagy inhibitor.
  • the autophagy regulating method of the autophagy regulator of the present invention is: mixing sample cells with the autophagy regulator and incubating them, destroying the mitochondria of the sample cells to induce mitochondrial autophagy; and destroying the lysosomes of the sample cells to inhibit the autophagy flow.
  • the mitochondrial membrane potential is reduced.
  • the pH of the lysosomes increases.
  • the autophagy regulator provided by the present invention is a dual-targeted fluorescent organic small molecule autophagy activator and autophagy inhibitor.
  • the dual-targeted fluorescent organic small molecule of the present invention is unique in that it can simultaneously activate mitochondrial autophagy and destroy lysosomal function, inhibit autophagic flow, and thus kill cancer cells; it is also a new type of mitochondrial/lysosomal fluorescent probe, which can simultaneously target mitochondria and lysosomes compared with the existing mitochondrial and lysosomal fluorescent probes. It emits red fluorescence, images the morphology, quantity and distribution of mitochondria and lysosomes, and has good membrane permeability and good redyeing compatibility.
  • the dual-targeted fluorescent organic small molecule autophagy activator and autophagy inhibitor provided by the present invention can, on the one hand, be used as an autophagy regulator to activate mitochondrial autophagy and inhibit autophagy flux, thereby being used as an anticancer drug to kill cancer cells; on the other hand, it can be used as a fluorescent probe to mark the morphology, number and distribution of mitochondria and lysosomes in cells, and can provide a simple and intuitive biological detection reagent for physiological and pathological research related to mitochondria and lysosomes and clinical diagnosis, and has a wide range of applications and good effects.
  • the halogen atom is selected from any one of iodine, bromine and chlorine.
  • the C1-C4 alkyl group includes any one of a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group and a tert-butyl group.
  • the C1-C4 alkyl group includes any one of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl.
  • said C1-C4 alkyl group includes any one of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl.
  • the C1-C4 alkoxy group includes any one of a methoxy group, an ethoxy group, a propoxy group and a butoxy group.
  • the obtained autophagy regulator independent of mitochondrial membrane potential is (E)-4-(2-(5-methoxy-1H-indole-3-)vinyl)-1-n-dodecylquinoline iodide.
  • a method for preparing an autophagy regulator comprises the following steps:
  • the catalyst includes piperidine.
  • the solvent comprises ethanol.
  • the molar ratio of indole-3-carboxaldehyde to 4-methylquinoline is 1:(1.0-2.0).
  • the reflux reaction time is 3 to 4 days.
  • the reflux reaction time is 1 to 2 days.
  • the indole-3-carboxaldehyde is selected from 5-methoxy-3-formyl indole; the alkyl halide is selected from iododecane, and the autophagy regulator is prepared by using 5-methoxy-3-formyl indole and iododecane as reactants as follows:
  • the organic solid product to be purified is purified by column chromatography, using dichloromethane/methanol as eluent, and dried to obtain dark green crystals and dark red powder.
  • the dark green crystals and dark red powder are dual-targeted fluorescent organic small molecule autophagy activator and autophagy inhibitor.
  • the dual-targeted fluorescent organic small molecule autophagy activator and autophagy inhibitor is (E)-4-(2-(5-methoxy-1H-indole-3-)vinyl)-1-n-dodecylquinoline iodide.
  • an autophagy regulator is used in the preparation of a related life form for regulating cell autophagy Application in active products.
  • the dual-targeted fluorescent organic small molecule autophagy activator and autophagy inhibitor is used to regulate cell autophagy for non-diagnostic and therapeutic purposes.
  • the dual-targeted fluorescent organic small molecule of the present application can target the mitochondria and lysosomes of the cells, causing the mitochondrial membrane potential to decrease or even be lost, thereby inducing mitochondrial autophagy and generating a large number of autophagosome vesicles; at the same time, the lysosomal pH rises and cannot fuse with the autophagosome to form autophagic lysosomes, thereby inhibiting the completion of the autophagic flow and achieving dual regulation of autophagy.
  • an autophagy regulator is used in the preparation of a product for targeting mitochondria or lysosomes.
  • the method of using an autophagy regulator to perform mitochondrial/lysosomal fluorescence imaging in the present invention comprises: mixing and incubating sample cells with an autophagy regulator, wherein the autophagy regulator binds to the mitochondria and lysosomes of the sample cells, and the fluorescence intensity is enhanced to achieve fluorescence imaging of the mitochondria and lysosomes.
  • the present invention provides an application of a dual-targeted fluorescent organic small molecule autophagy activator and autophagy inhibitor for mitochondrial/lysosomal fluorescence imaging.
  • the dual-targeted fluorescent organic small molecule can simultaneously target cell mitochondria and lysosomes. After binding to mitochondria and lysosomes, the fluorescence is greatly enhanced, thereby realizing the application of simultaneous fluorescence imaging of mitochondria and lysosomes.
  • the dual-targeted fluorescent organic small molecule autophagy activator and autophagy inhibitor in the present invention is used for mitochondrial/lysosomal fluorescence imaging for non-diagnostic and therapeutic purposes.
  • the dual-targeted fluorescent organic small molecule in the present application does not fluoresce itself. After binding to mitochondria and lysosomes, the fluorescence is greatly enhanced, thereby realizing the application of simultaneous fluorescence imaging of mitochondria and lysosomes.
  • a drug for treating tumors includes a cell autophagy regulating drug, and the cell autophagy regulating drug includes the autophagy regulator.
  • the tumor comprises a tumor overexpressing albumin receptor.
  • the tumors overexpressing albumin receptors include cervical cancer, breast cancer, ovarian cancer, melanoma, pancreatic cancer, liver cancer, etc.
  • the medicament comprises an injectable composition or a composition for oral administration.
  • the composition includes a dual-targeted fluorescent organic small molecule autophagy activator and autophagy inhibitor and other pharmaceutically acceptable carriers, wherein the carrier includes but is not limited to various pharmaceutical excipients.
  • the method of using the autophagy regulator to kill cancer cells in the present invention comprises: mixing and incubating sample cells with the autophagy regulator, activating mitochondrial autophagy, inhibiting lysosomal function and autophagy, and inducing death of the sample cells.
  • the autophagy regulator of the present invention has dual-targeted fluorescent organic small molecules for autophagy activation and Autophagy inhibitors have dual targeting effects and can simultaneously target cell mitochondria and lysosomes, activating mitochondrial autophagy and inhibiting lysosomal function, ultimately leading to cell death.
  • This dual-targeted fluorescent organic small molecule autophagy activator and autophagy inhibitor can be used to kill cancer cells, realizing the application of dual-targeted fluorescent organic small molecule autophagy activator and autophagy inhibitor as autophagy regulator and cancer cell killer.
  • Figure 1 is a fluorescence micrograph of HeLa cells co-stained with (E)-4-(2-(5-methoxy-1H-indole-3-)vinyl)-1-n-dodecylquinoline iodide and mitochondrial green fluorescent probe (MitoTracker Green) and lysosomal deep red fluorescent probe (LysoBrite NIR) provided in Example 3 of the present application.
  • FIG2 is a fluorescence micrograph of HeLa cells stained with rhodamine 123 after being treated with (E)-4-(2-(5-methoxy-1H-indol-3-)vinyl)-1-n-dodecylquinoline iodide provided in Example 4 of the present application.
  • Figure 3 is a fluorescence micrograph of lysosomal green fluorescent probe (Lysosensor Green DND-189) staining of HeLa cells treated with (E)-4-(2-(5-methoxy-1H-indol-3-)vinyl)-1-n-dodecylquinoline iodide provided in Example 5 of the present application.
  • Figure 5 is a fluorescence micrograph of the staining of mitochondria and lysosomes of HeLa cells after being treated with (E)-4-(2-(5-methoxy-1H-indole-3-)vinyl)-1-n-dodecylquinoline iodide and CCCP, respectively, as provided in Test Example 6 of the present application.
  • FIG6 is a fluorescence micrograph of HeLa cells incubated at 37° C. and 4° C. with (E)-4-(2-(5-methoxy-1H-indole-3-)vinyl)-1-n-dodecylquinoline iodide provided in Test Example 7 of the present application.
  • FIG. 7 is a microscopic photograph of normal cell spheres HEK293 and cancer cell spheres HeLa before and after incubation with (E)-4-(2-(5-methoxy-1H-indole-3-)vinyl)-1-n-dodecylquinoline iodide provided in Test Example 8 of the present application.
  • the term "and/or” describes the association relationship of associated objects, indicating that there may be three relationships.
  • a and/or B can mean: A exists alone, A and B exist at the same time, and B exists alone.
  • a and B can be singular or plural.
  • the character "/" generally indicates that the associated objects are in an "or” relationship.
  • At least one means one or more
  • plural means two or more.
  • At least one of the following” or similar expressions refers to any combination of these items, including any combination of single items or plural items.
  • at least one of a, b, or c or “at least one of a, b, and c” can all mean: a, b, c, a-b (i.e. a and b), a-c, b-c, or a-b-c, where a, b, and c can be single or multiple, respectively.
  • the size of the serial numbers of the above-mentioned processes does not mean the order of execution, some or all of the steps can be executed in parallel or sequentially, and the execution order of each process should be determined by its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of the present application.
  • the weight of the relevant components mentioned in the embodiment description of the present application can not only refer to the specific content of each component, but also represent the proportional relationship between the weights of the components. Therefore, as long as the content of the relevant components is proportionally enlarged or reduced according to the embodiment description of the present application, it is within the scope disclosed in the embodiment description of the present application.
  • the mass described in the embodiment description of the present application can be a mass unit known in the chemical industry such as ⁇ g, mg, g, kg, etc.
  • the mixture is slowly cooled, filtered, and washed with a small amount of isopropanol to obtain dark green crystals or dark red powder, or excess solvent is evaporated, cooled, and the product is purified by column chromatography using dichloromethane/methanol as an eluent to obtain dark green crystals and dark red powder, with a yield of about 27%.
  • R 3 can also be selected from any one of hydrogen, C1-C4 alkyl, C1-C4 alkoxy, and R 2 is selected from any one of hydrogen or C1-C4 alkyl.
  • the function of the autophagy regulator in the present invention is determined by the conjugated organic cationic group and has nothing to do with the anion X- ;
  • R 2 is selected from any one of hydrogen or C1-C4 alkyl;
  • R 3 is selected from any one of hydrogen, C1-C4 alkyl, and C1-C4 alkoxy.
  • indoloctyl quinoline salt has a weak binding effect on albumin and still enters the cell in a free diffusion manner.
  • the binding effect with albumin is enhanced and enters the cell in an active transport manner.
  • Cancer cells HeLa and normal cells HEK293 were cultured in complete culture medium (DMEM culture medium containing 10% fetal bovine serum and 1% penicillin/streptomycin) at 37°C in a saturated humidity incubator with 5% CO 2 , and passaged every 2 to 3 days.
  • complete culture medium DMEM culture medium containing 10% fetal bovine serum and 1% penicillin/streptomycin
  • the HeLa cell-covered slide prepared in Test Example 1 was washed twice with PBS, and then the following staining steps were performed: (1) incubated with 0.5 ⁇ M commercial mitochondrial green fluorescent probe (MitoTracker Green) solution for 30 min, and washed with PBS; (2) incubated with 0.5 ⁇ M commercial lysosomal near-infrared fluorescent probe (LysoBrite NIR) solution for 30 min, and washed with PBS; (3) incubated with 2 ⁇ M (E)-4-(2-(5-methoxy-1H-indole-3-)vinyl)-1-n-dodecylquinoline iodide fluorescent probe solution for 30 min, and washed with DMEM. The stained cell samples were observed for multi-channel fluorescence co-localization using a confocal fluorescence microscope.
  • Figure 1 (A) is a red fluorescence image of the molecule synthesized in Example 1
  • Figure 1 (B) is a fluorescence image of a commercial mitochondrial green fluorescent probe
  • Figure 1 (C) is a fluorescence image of a commercial lysosomal near-infrared fluorescent probe
  • Figure 1 (D) is an overlay of Figure 1 (A), Figure 1 (B), and Figure 1 (C).
  • Figure 1 (A) covers the two regions of Figure 1 (B) and Figure 1 (C), and the sum of Figure 1 (A), Figure 1 (B), and Figure 1 (C) overlap well, indicating that the fluorescence of the molecule synthesized in Example 1 is distributed in two organelles, mitochondria and lysosomes.
  • Figure 2 is a fluorescence micrograph of the mitochondrial membrane potential probe rhodamine 123 before and after the synthetic molecule of Example 1 is treated on HeLa cells.
  • Figure 2(A) is a fluorescence micrograph of cells in the blank control sample group;
  • Figure 2(B) is a bright field micrograph corresponding to Figure 2(A);
  • Figure 2(C) is a fluorescence micrograph of rhodamine 123 of cells treated with the synthetic molecule of Example 1;
  • Figure 2(D) is a bright field micrograph corresponding to Figure 2(C).
  • Figure 3 is a fluorescence micrograph of the lysosomal green fluorescent probe (LysoSensor Green DND-189) before and after the synthetic molecule in Example 1 treated HeLa cells.
  • Figure 3(A) is a fluorescence micrograph of cells in the blank control sample group;
  • Figure 3(B) is a bright field micrograph corresponding to Figure 3(A);
  • Figure 3(C) is a fluorescence micrograph of the lysosomal green fluorescent probe of cells treated with the synthetic molecule in Example 1;
  • Figure 3(D) is a bright field micrograph corresponding to Figure 3(C).
  • the fluorescence of LysoSensor Green DND-189 will increase with the decrease of pH.
  • Figure 4 is a fluorescence micrograph of the green live cell tracer probe (Cell-Tracker Green CMFDA) before and after the synthetic molecule in Example 1 treated HeLa cells
  • Figure 4 (A) is a fluorescence micrograph of the cells in the blank control sample group
  • Figure 4 (B) is a fluorescence micrograph of the green live cell tracer probe of the cells treated with the synthetic molecule in Example 1. Comparing Figures 4 (A) and 4 (B), a large number of vacuoles (autophagic vacuoles and autophagosomes) were generated in the cytoplasm of the cells treated with the synthetic molecule in Example 1, indicating that the synthetic molecule in Example 1 can activate cell autophagy.
  • vacuoles autophagic vacuoles and autophagosomes
  • Figure 5 is a fluorescence micrograph of mitochondria and lysosomes of HeLa cells treated with the synthetic molecules of Example 1
  • Figure 5 (A) is a fluorescence micrograph of mitochondria of cells in the positive control sample group
  • Figure 5 (B) is a fluorescence micrograph of lysosomes of cells in the positive control sample group
  • Figure 5 (C) is an overlay of Figure 1 (A) and Figure 1 (B)
  • Figure 5 (D) is a fluorescence micrograph of mitochondria of cells treated with the synthetic molecules of Example 1
  • Figure 5 (E) is a fluorescence micrograph of lysosomes of cells treated with the synthetic molecules of Example 1
  • Figure 5 (F) is an overlay of Figure 1 (D) and Figure 1 (E).
  • Figures 6(A) and 6(B) are red fluorescence micrographs of HeLa cells incubated with (E)-4-(2-(5-methoxy-1H-indol-3-)vinyl)-1-n-dodecylquinoline iodide at 37°C and 4°C, respectively.
  • the fluorescence intensity of Figure 6(A) is significantly greater than that of Figure 6(B), indicating that the main way in which (E)-4-(2-(5-methoxy-1H-indol-3-)vinyl)-1-n-dodecylquinoline iodide enters the cell is active transport.
  • Test Example 8 The test results of Test Example 8 are shown in Figure 7.
  • Figures 7(A) and 7(B) are bright field micrographs of HEK293 cell spheres before incubation and administration
  • Figures 6(C) and 6(D) are bright field micrographs of HeLa cell spheres before incubation and administration
  • Figures 7(E) and 7(G) are bright field micrographs of HEK293 cell spheres and HeLa cell sphere blank control groups after 24 hours, respectively
  • Figures 7(F) and 7(H) are bright field micrographs of HEK293 cell spheres and HeLa cell spheres after incubation and administration for 24 hours, respectively.
  • Example 2 Different concentrations of the molecule synthesized in Example 1 (0-15 ⁇ M) were added to a PBS solution of bovine serum albumin, and then the fluorescence spectrum of the albumin (280 nm EX) was measured using a fluorescence spectrometer.
  • FIG8 (A) is the fluorescence spectrum of albumin with different concentrations of the molecules synthesized in Example 1 (0-15 ⁇ M)
  • FIG8 (B) is a double logarithmic fitting curve of the fluorescence intensity reduction degree and the concentration of the molecules synthesized in Example 1 made according to FIG8 (A). It can be seen from FIG8 (A) that with the increase in the concentration of the molecules synthesized in Example 1, the fluorescence peak of albumin gradually decreases. According to the fitting curve FIG8 (B), it is concluded that the binding constant between the molecules synthesized in Example 1 and albumin is as high as 1.35 ⁇ 10 8 .
  • the present application provides a dual-targeted fluorescent organic small molecule autophagy regulator and its application.
  • the dual-targeted fluorescent organic small molecule autophagy regulator of the present invention can simultaneously target mitochondria and lysosomes, on the one hand, destroying mitochondria to activate mitophagy, and on the other hand, alkalizing the pH of lysosomes, preventing the fusion of mitochondria and lysosomes, and inhibiting the autophagy flow.
  • the fluorescence is greatly enhanced after targeting mitochondria and lysosomes, and the synchronous fluorescence visualization of mitochondria and lysosomes is achieved.

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Abstract

La présente invention concerne un régulateur d'autophagie, son procédé de préparation et son utilisation. L'invention concerne un activateur d'autophagie à petite molécule organique fluorescent à ciblage double et un inhibiteur d'autophagie et leur utilisation pour résoudre les problèmes qui se posent dans l'état de la technique pour la régulation de l'autophagie, en raison d'un ciblage unique, de l'absence de sélectivité cellulaire et des effets limités de destruction des cellules cancéreuses.
PCT/CN2023/135725 2023-11-30 2023-11-30 Régulateur d'autophagie, son procédé de préparation et son utilisation Pending WO2025112010A1 (fr)

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Citations (3)

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Publication number Priority date Publication date Assignee Title
CN106833623A (zh) * 2017-02-17 2017-06-13 广东工业大学 一种荧光探针及其制备方法
US20200378979A1 (en) * 2019-05-31 2020-12-03 University Of Guelph Fluorescent merocyanine dyes, associated conjugates and methods
CN112402608A (zh) * 2020-11-30 2021-02-26 深圳先进技术研究院 5-烷氧基吲哚-3-乙烯基喹啉盐作为靶向可迁移光敏剂的应用

Patent Citations (3)

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Publication number Priority date Publication date Assignee Title
CN106833623A (zh) * 2017-02-17 2017-06-13 广东工业大学 一种荧光探针及其制备方法
US20200378979A1 (en) * 2019-05-31 2020-12-03 University Of Guelph Fluorescent merocyanine dyes, associated conjugates and methods
CN112402608A (zh) * 2020-11-30 2021-02-26 深圳先进技术研究院 5-烷氧基吲哚-3-乙烯基喹啉盐作为靶向可迁移光敏剂的应用

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Title
KRIEG, R. ET AL.: "N,N-dialkylaminostyryl Dyes: Specific and Highly Fluorescent Substrates of Peroxidase and Their Application in Histochemistry", JOURNAL OF MOLECULAR HISTOLOGY, vol. 39, no. 2, 29 November 2007 (2007-11-29), pages 169 - 191, XP019573294 *
LU, YUJING ET AL.: "Selective Visualization of DNA G-Quadruplex Structures in Live Cells with 1-Methylquinolinium-Based Molecular Probes: The Importance of Indolyl Moiety Position Towards Specificity", DYES AND PIGMENTS, vol. 143, 20 April 2017 (2017-04-20), pages 331 - 341, XP055819003, DOI: 10.1016/j.dyepig.2017.04.038 *
SONG, GUOFEN ET AL.: "Mitochondria/RNA Cascade-Targeted and Fluorescence-Switchable Photosensitizer for Photodynamic Therapy Augmentation and Real-Time Efficacy Self-Monitoring", SENSORS AND ACTUATORS: B. CHEMICAL, vol. 369, 20 June 2022 (2022-06-20), XP087138417, DOI: 10.1016/j.snb.2022.132260 *

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