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Article

Aggregation-Induced Luminescent 3-Phenylpyrano[4,3-b]quinolizine Derivatives as Photosensitizers with Anti-Cancer Properties

by
Masayori Hagimori
1,*,
Tatsusada Yoshida
2,
Takuma Tsutsumi
2,
Fumiko Hara
1,
Shinya Takada
1,
Yukiko Ogawa
2 and
Keitaro Tanaka
3
1
Faculty of Pharmaceutical Sciences, Mukogawa Women’s University, 11-68 Koshien 9-Bancho, Nishinomiya 663-8179, Hyogo, Japan
2
Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo 859-3298, Nagasaki, Japan
3
Saiki Central Hospital Pharmacy, 6-30 Tokiwa Higashi-machi, Saiki 876-0851, Oita, Japan
*
Author to whom correspondence should be addressed.
Molecules 2025, 30(7), 1422; https://doi.org/10.3390/molecules30071422
Submission received: 28 February 2025 / Revised: 20 March 2025 / Accepted: 21 March 2025 / Published: 23 March 2025
(This article belongs to the Special Issue Design, Synthesis and Evaluation of Novel Anticancer Agents, 2nd Edition)
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Abstract

Photodynamic therapy (PDT) has garnered significant attention as an effective and safe method for cancer therapy, with ongoing efforts to develop new photosensitizers to enhance its efficacy. This study aimed to develop novel photosensitizers with aggregation-induced emission enhancement (AIEE) properties. A series of 3-phenyl pyrano[4,3-b]quinolizine compounds (3–10) were synthesized by reacting pyrones (1a–e) with 2-pyridylacetate (2a) or 2-pyridylacetonitrile (2b) and then evaluated for their potential as photosensitizers. Spectroscopic analyses revealed that all compounds emitted blue to green fluorescence in ethanol, with emission wavelengths ranging from 446 nm to 515 nm. Compounds 5 and 6, lacking a substituent at position 5 of pyrano[4,3-b]quinolizine, exhibited AIEE behavior in aqueous solution. Furthermore, all compounds produced reactive oxygen species upon exposure to LED light. Notably, compounds 5 and 6 demonstrate high singlet oxygen (1O2) generation efficiency in water-rich solvents, where they tend to aggregate, contributing to their potential to destroy cancer cells. In vitro studies using human colon cancer cells (Colo205) demonstrated that 5 and 6 exhibited potent anti-tumor activity upon exposure to LED light. These findings suggest that compounds 5 and 6, based on 3-phenyl pyrano[4,3-b]quinolizine, possessing AIEE properties, are potential new photosensitizers for PDT.

1. Introduction

Fluorescent materials are extensively utilized in the fields of life sciences and medicine owing to their high sensitivity and the ability to derive various information from their excitation and fluorescence spectra [1,2,3]. These materials are derived from small organic molecules, proteins, quantum dots, and others [4,5]. Small organic molecules are relatively easy to modify structurally and introduce substituents, enabling the optimization of emission intensity and wavelength according to the intended purpose, displaying characteristic fluorescence in dilute solutions [6,7,8]. However, at concentrations above a certain threshold, many fluorescent molecules tend to aggregate and quench, a phenomenon known as aggregation-caused quenching (ACQ) [9,10]. Consequently, the occurrence of ACQ in aqueous solutions raises concerns, as it may lead to unexpected outcomes in biological applications. In contrast, aggregation-induced emission enhancement (AIEE) dyes based on small organic molecules have been developed, and these dyes retain their fluorescence even after aggregation [11,12,13]. As a result, these AIEE dyes hold promise for diverse applications in various fields, including biology.
Cancer is one of the main causes of mortality worldwide, and conquering it is a desirable goal [14]. The primary treatments for cancer include surgery, chemotherapy, radiotherapy, and immunotherapy, either alone or in combination [15]. However, each treatment modality presents unique challenges, such as invasiveness, side effects, resistance, and lengthy treatment durations, necessitating the development of new cancer treatment modalities. Photodynamic therapy (PDT) is one of the treatment modalities that utilize the reaction induced by light irradiation on agents accumulated in the cancerous tissue [15]. PDT has garnered attention as a cancer-specific treatment in recent years. The agents used in PDT are photosensitizers that produce reactive oxygen species (ROS) upon exposure to light of particular wavelengths, facilitating the targeted destruction of cancer cells. Generally, ROS generated by photosensitizers fall into two categories: Type I, which yields superoxide anion (O2•−) and hydroxyl radical (•OH), and Type II, which produces singlet oxygen (1O2) [16,17]. In clinical settings, porphyrin derivatives such as talaporfin sodium and redaporfin are commonly utilized due to their efficient generation of 1O2 upon light exposure and proven efficacy in the treatment of various cancers, including breast cancer, melanoma, and head and neck cancer [18,19,20]. However, these photosensitizers have a tendency to aggregate in aqueous solutions, leading to reduced ROS production. Consequently, alternative agents are being developed to replace porphyrin derivatives. In this respect, AIEE dyes hold promise for stable ROS generation, even in an aggregated state. In recent years, attempts have been undertaken to develop photosensitizers based on this phenomenon [21,22,23].
In this study, to develop novel photosensitizers based on AIEE, we synthesized a series of 3-phenyl pyrano[4,3-b]quinolizine compounds (3–10). Pyrano[4,3-b]quinolizine is a tricyclic compound known for its fluorescence properties when electron-donating or electron-withdrawing groups are introduced. It has been utilized in fluorescent probes for targeting metal ions in biological and environmental samples [24,25]. Among these derivatives, compounds 5 and 6, lacking a substituent at position 5 of pyrano[4,3-b]quinolizine, exhibited AIEE characteristics in aqueous media. This study reports the synthesis, photophysical properties, LED light-induced generation of ROS, and anti-tumor activity of the 3-phenyl pyrano[4,3-b]quinolizine compounds.

2. Results and Discussion

As shown in Scheme 1, 3-phenylpyrano[4,3-b]quinolizine compounds (3–10) were synthesized by reacting pyrones (1a–e) with 2-pyridylacetate (2a) or 2-pyridylacetonitrile (2b) using a previously reported synthetic method [24]. In dimethyl sulfoxide (DMSO), 1a and 2a were mixed with potassium carbonate as the base. After 2 h, neutralization of the mixture with 10% hydrochloric acid yielded the dicarbonyl compound, methyl 1,11-dioxo-3-phenyl-1H,11H-pyrano[4,3-b]quinolizine-5-carboxylate (3), with an 86% yield. Similarly, the dicarbonyl compound 4 was obtained in an 83% yield from the reaction of 1b and 2a. Decarboxylated compounds (5 and 6) were obtained in good yield by treating the corresponding 3-phenylpyrano[4,3-b]quinolizines (3 and 4) with polyphosphoric acid (PPA), respectively. Imino carbonyl compounds (7 and 8) and dicarbonyl compounds with a cyano group (9 and 10) were synthesized with yields ranging from 72% to 93% using the same synthetic method as compound 3. The molecular structures of 3–10 were verified through 1H- and 13C-NMR (Figures S1–S16 in the Supplementary Materials File).
Spectroscopic studies of compounds 3–10 in ultraviolet/visible (UV/Vis) and fluorescence were conducted in ethanol (EtOH) (Figures S17 and S18 in Supplementary Materials File). Table 1 lists the spectroscopic properties, including the maximum value of absorption wavelength (λmax), molar extinction coefficient (log ε), emission maximum (Emmax), Stokes shift (SS), and quantum yield of fluorescence (Φ). The λmax of dicarbonyl compounds 3–6, 9, and 10 ranged from 432 to 445 nm in EtOH. In contrast, the λmax of imino carbonyl compounds 7 and 8 exhibited a hypsochromic shift at 366 and 368 nm, respectively. Additionally, the log ε of compounds 7 and 8 was lower than that of compounds 3–6, 9, and 10, suggesting that they are influenced by the structural or electronic effects of the imino group at position 1 on pyrano[4,3-b]quinolizine. Regarding fluorescence, all compounds exhibited blue to green fluorescence ranging from 446 nm to 515 nm. Compounds 4, 6, and 10, with a methoxy group at position 3 of pyrano[4,3-b]quinolizine, exhibited a bathochromic shift of 4–64 nm compared to compounds 3, 5, and 9 without a methoxy group. In contrast, de-esterification of compounds 3 and 4 led to a hypsochromic shift in Emmax for compounds 5 and 6, accompanied by decreased Φ values (0.11 and 0.03, respectively). In compounds 4 and 7 with ester groups, the introduction of an imino group did not significantly alter fluorescence properties (Emmax and Φ values). However, in comparison to compounds 8 and 10 with cyano groups, the imino group shifted the fluorescence wavelength 44 nm towards longer wavelengths. Imino carbonyl compounds 7 and 8 exhibited large SS values exceeding 100 nm. Generally, the SS of organic fluorophores is in 10 s of nm, with values greater than 100 nm reported for lanthanide chelate complexes, nanoparticles, and proteins that exhibit fluorescence. A large SS is advantageous as it minimizes the effect of light scattering during fluorescence measurements [26].
The AIEE behaviors of 3-phenylpyrano[4,3-b]quinolizine compounds (3–10) were investigated in various EtOH/H2O (v/v) solvent mixtures (Figure 1). The fluorescence intensity of compounds 3, 4, and 7–10 decreased as the water ratio in the solvent increased. The fluorescence intensity at Emmax for each compound was plotted (insets in Figure 1) and was completely quenched when the solvent was nearly all water (95% water). This phenomenon is attributed to ACQ, resulting from aggregate formation with increasing water content in the measurement solvent. In contrast, compounds 5 and 6 exhibited consistent fluorescence intensity even in solvents with 90% or 95% water, showing no significant decrease with an increasing water ratio. A dynamic light scattering (DLS) study was conducted to examine whether compounds 3–10 aggregate as the water ratio in the solvent increases. All compounds increased in size as the water ratio increased, as shown in Table 2, suggesting that the fluorescence of compounds 5 and 6 in high-water-ratio solutions is due to AIEE. Furthermore, compounds 5 and 6 lack a substituent at position 5 of pyrano[4,3-b]quinolizine, indicating that this position of pyrano[4,3-b]quinolizine is primarily responsible for the AIEE effect.
To evaluate the ROS generation following LED light exposure of 3-phenylpyrano[4,3-b]quinolizine compounds (3–10), we used the Amplite™ ROS Red total ROS detection sensor. Total ROS includes O2•−, •OH, hydrogen peroxide, 1O2, nitric oxide, and other related species. The fluorescence intensity at 605 nm of the sensor increases upon ROS production in the solution. After exposing the mixture of the sensor and each compound in acetonitrile to 365 nm LED light (1.7 W) for 2 min, the fluorescence spectrum excited at 520 nm was recorded. Compared to the fluorescence intensity of the sensor-only solution used as a control, an increase in fluorescence intensity was observed for all compounds, indicating ROS generation (Figure 2). Notably, compounds 5 and 6 exhibited 5.0- and 7.3-fold higher fluorescence intensity, respectively, relative to the control, signifying significant ROS generation. Given that the 1O2 is highly reactive and the major ROS responsible for cancer cell destruction in PDT, its generation was subsequently investigated [16,17]. 1,3-Diphenylisobenzofuran (DPBF) serves as a common 1O2 scavenger [27], with its absorption at 405 nm decreasing upon reaction with 1O2. Solutions of DPBF and each compound in acetonitrile were irradiated in a 96-well-plate with 365 nm LED light (1.7 W). The degradation of DPBF over LED light exposure time was tracked up to 180 sec via UV/Vis absorption. The degradation of DPBF in acetonitrile is illustrated by the solid line in Figure 3, indicating that all compounds generate 1O2. The observed rate constants and 1O2 quantum yield (ΦΔ) in acetonitrile are listed in Table 3. The ΦΔ values in acetonitrile ranged from 0.53 to 0.91, with compounds 5 and 6 displaying relatively lower values of 0.53 and 0.67, respectively. The higher values of total ROS generation for compounds 5 and 6 in acetonitrile shown in Figure 2 may be due to the contribution of various ROS other than 1O2. Conversely, in acetonitrile/water 50:50 (v/v) (Figure 3, dotted line), the degradation of DPBF was more pronounced for compounds 5 and 6 than in acetonitrile alone. These findings suggest that compounds 5 and 6 lack a substituent at position 5 of pyrano[4,3-b]quinolizine, absorb light, and generate higher levels of singlet oxygen in environments with elevated water contents, where molecular aggregation is more probable.
The anti-tumor activity of compounds 3–10 as a photosensitizer in PDT was investigated using human colon cancer cells (Colo205). Colo205 cells were treated with compounds 3–10 at different concentrations for 4 h and then exposed to 365 nm LED light (482.4 mW) for 300 sec. Following an additional 48 h of incubation, the anti-tumor activity of 3–10 was assessed using the WST-8 assay. For all compounds, the cell viability in the non-irradiated LED group remained above 80%, and no significant effects were observed (Figure S19). As depicted in Figure 4, compounds 5 and 6 exhibited significant anti-tumor effects on Colo205 cells, with half maximal inhibitory concentrations (IC50) of 20.1 µM and 23.8 µM, respectively. The lack of anti-tumor effects in cells not exposed to LED light post-treatment with compounds 5 and 6 indicates that the anti-tumor activity was induced by 1O2 generation upon light exposure. These results suggest that compounds 5 and 6, possessing AIEE properties, could serve as promising photosensitizers for PDT. However, further investigations, including assessments with other cancer cell lines, are warranted.

3. Materials and Methods

3.1. Reagents and Instruments

The materials and reactants utilized in this study were purchased from suppliers and utilized without purification if not specifically required. The following equipment were used in the identification and quantification of 3-phenyl pyrano[4,3-b]quinolizine compounds. A Yanako MP-500D (Kyoto, Japan) was used to determine the melting points. The JEOL JNM-EPC 400 (Tokyo, Japna) and JNM-ECA 500 (Tokyo, Japna) spectrometers were utilized to obtain the NMR spectrum. The JMS-700 mass spectrometer (JEOL, Tokyo, Japan) was used to acquire mass spectra (MS) and high-resolution mass spectrometry (HRMS). UV/Vis absorption data were acquired with a UV-2450 spectrometer (Shimadzu, Kyoto, Japan). The fluorescence data were acquired by an FP-8300 spectrometer (JASCO, Tokyo, Japan).

3.2. Synthetic Method of Methyl 1,11-dioxo-3-phenyl-1H,11H-pyrano[4,3-b]quinolizine-5-carboxylate (3) [24]

To a mixture of 0.55 g of pyrone 1a (2.0 mmol) and 0.45 g of methyl 2-pyridylacetate 2a (3.0 mmol) in 20 mL of DMSO, 0.67 g of potassium carbonate (5.0 mmol) was mixed and stirred at room temperature. After 2 h of stirring, the mixture was reacted for a further 20 min at 50–60 °C. Subsequently, 200 mL of ice water was added into the mixture, leading to the generation of a precipitate that was collected through filtration and rinsed with water. Recrystallization using DMF gave 3 (0.59 g, 1.7 mmol) of orange needles in 86% yield. Melting point: 239–241 °C. 1H NMR (400 MHz, CDCl3) δ: 9.39 (d, J = 5.8 Hz, 1H), 8.09 (d, J = 8.8 Hz, 1H), 7.91 (m, 2H), 7.74 (m, 1H), 7.48 (m, 3H), 7.24 (m, 1H), 7.21 (s, 1H) 4.08 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 175.1, 166.3, 159.6, 158.6, 154.9, 146.3, 145.7, 136.5, 131.4, 131.3, 130.1, 128.9, 126.2, 123.7, 116.2, 101.2, 97.9, 96.7, 52.6. MS spectrum (ESI, m/z): 348 (M++1), 347 (M+). HRMS (ESI, m/z): Calcd. for C20H13NO5, 347.0794 (M+); found, 347.0793.

3.3. Synthetic Method of Methyl 1,11-dihydro-3-(4-methoxy)phenyl-1,11-dioxoyrano[4,3-b]quinolizine-5-carboxylate (4) [24]

The desired compound 4 (0.31 g, 0.83 mmol) was synthesized with an 83% yield from 0.31 g of 1b (1.0 mmol) and 0.22 g of 2-pyridylacetonitrile 2b (1.5 mmol) following a procedure similar to the synthetic method of 3. The sample for analysis was recrystallized from DMF to obtain yellow needles, with a melting point of 256–260 °C. 1H NMR (400 MHz, CDCl3) δ: 9.39 (d, J = 3.0 Hz, 1H), 8.06 (d, J = 8.0 Hz, 1H), 7.86 (m, 1H), 7.70 (m, 1H), 7.17 (m, 1H), 7.13 (s, 1H), 7.00 (m, 2H), 4.07 (s, 3H), 3.88 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 166.4, 162.2, 159.7, 158.7, 154.9, 146.6, 145.7, 136.3, 130.1, 128.4, 128.0, 123.6, 115.9, 114.3, 100.9, 96.3, 55.6, 52.6. MS spectrum (ESI, m/z): 378 (M++1), 377 (M+). Anal. Calcd. for C21H15NO6 377.0899: C 66.84 H, 4.01; N 3.71. Found: C, 66.79; H, 4.12; N, 3.59.

3.4. Synthetic method of 1,11-dihydro-3-phenylpyrano[4,3-b]quinolizine-1,11-dione (5) [24]

A mixture of 1.74 g of 3 (5.0 mmol) and 30 g of PPA was heated with stirring at 100 °C for 1 h. Upon adding ice water to the mixture, the resulting residue was collected through filtration and rinsed with water. Recrystallization using DMF gave 5 (1.21 g, 4.2 mmol) of orange needles in 84% yield. Melting point: 256–257 °C. 1H NMR (400 MHz, CDCl3) δ: 9.22 (d, J = 6.8 Hz, 1H), 7.94 (d, J = 7.8 Hz, 1H), 7.89 (m, 2H), 7.54 (m, 1H), 7.46 (m, 3H), 7.02 (m, 1H), 6.70 (s, 1H), 6.47 (s, 1H). 13C NMR (100 MHz, CDCl3) δ: 158.9, 155.8, 149.1, 146.8, 146.1, 134.3, 131.3, 130.9, 129.5, 129.4, 128.8, 126.9, 125.9, 125.1, 122.5, 115.2, 99.7, 98.4. MS spectrum (ESI, m/z): 290 (M++1), 289 (M+). HRMS (ESI, m/z): Calcd. for C18H11NO3, 289.0739 (M+); found, 289.0743.

3.5. Synthetic Method of 1,11-dihydro-3-(4-methoxy-phenyl)-pyrano[4,3-b]quinolizine-1,11-dione (6) [24]

The desired compound 6 (0.28 g, 0.88 mmol) was synthesized with an 88% yield from 0.38 g of 4 (1.0 mmol) and 30 g of PPA following a procedure similar to the synthesis of 5. The sample for analysis was recrystallized from DMF to obtain yellow needles, with a melting point of 214–216 °C. 1H NMR (400 MHz, DMSO-d6) δ: 9.03 (d, J = 7.3 Hz, 1H), 7.98 (d, J = 7.3 Hz, 1H), 7.81 (d, J = 8.3 Hz, 1), 7.75 (m, 1H), 7.28 (m, 1H), 7.26 (d, J = 8.3 Hz, 2H), 7.07 (s, 1H), 6.69 (s, 1H), 3.83 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ: 161.4, 157.9, 156.7, 154.9, 146.0, 135.4, 127.0, 125.6, 120.5, 116.3, 99.9, 95.2, 55.5. MS spectrum (ESI, m/z): 320 (M++1), 319 (M+). HRMS (ESI, m/z): Calcd. for C19H13NO4, 319.0845 (M+); found, 319.0851.

3.6. Synthetic Method of Methyl 1,11-dihydro-11-imino-3-(4-methoxyphenyl)-1-oxopyrano[4,3-b]quinolizine-5 carboxylate (7) [24]

To a mixture of 0.55 g of 1c (2.0 mmol) and 0.30 g of 2a (2.0 mmol) in 10 mL of DMSO, 0.12 g of potassium carbonate (0.9 mmol) was added and stirred at room temperature. After 2 h of stirring, the mixture was stirred for another 30 min at 50–60 °C. Subsequently, 200 mL of ice water was poured into the reaction mixture, leading to the formation of a precipitate that was collected through filtration and rinsed with water. Recrystallization using DMF gave 0.54 g of 7 (1.4 mmol) of orange needles in 72% yield. Melting point: 244–245 °C. 1H NMR (400 MHz, CDCl3) δ: 10.38 (br s, 1H), 9.72 (d, J = 6.6 Hz, 1H), 8.05 (dd, J = 1.5, 9.1 Hz, 1H), 7.85 (d, J = 9.1 Hz, 2H), 7.62 (ddd, J = 1.5, 6.6, 9.1 Hz, 1H), 7.26 (s, 1H), 7.03 (dd, J = 6.6, 6.6 Hz, 1H), 6.99 (d, J = 9.1 Hz, 2H), 4.00 (s, 3H), 3.90 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 166.8, 162.2, 161.9, 158.4, 152.9, 146.9, 144.8, 136.6, 131.2, 127.7, 123.9, 123.3, 115.0, 114.3, 97.4, 96.7, 95.0, 55.5, 52.1. MS spectrum (ESI, m/z): 377 (M++1), 376 (M+). Anal. Calcd. for C20H14N2O4 376.11: C, 67.02; H, 4.28; N, 7.44. Found: C, 66.83; H, 4.20; N, 7.32.

3.7. Synthetic Method of 1,11-dihydro-1-imino-3-(4-methoxyphenyl)-1-oxopyrano[4,3-b]quinolizine-5-carbonitrile (8) [24]

This desired compound 8 (0.58 g, 0.17 mmol) was synthesized with an 84% yield from 0.55 g of 1c (2.0 mmol) and 0.35 g of 2b (3.0 mmol) following a procedure similar to the synthesis of 7. The sample for analysis was recrystallized from DMF to obtain yellow needles, with a melting point of 280–282 °C. 1H NMR (400 MHz, CDCl3) δ: 10.48 (s, 1H), 9.13 (d, J = 7.2 Hz, 1H), 7.91 (d, J = 9.0 Hz, 2H), 7.82 (m, 1H), 7.16 (m, 1H), 7.01 (d, J = 9.0 Hz, 1H), 6.91 (s, 1H), 3.90 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 162.6, 161.1, 160.8, 151.9, 148.7, 146.5, 138.7, 131.7, 128.1, 123.0, 122.8, 116.5, 116.0, 114.5, 96.6, 95.0, 55.5. MS spectrum (ESI, m/z): 344 (M++1), 343 (M+). Anal. Calcd. for C20H13N3O3 343.34: C, 69.96; H, 3.82; N, 12.24. Found: C, 69.96; H, 3.78; N, 12.20.

3.8. Synthetic Method of 1,11-dioxo-3-phenyl-1H,11H-pyrano[4,3-b]quinolizine-5-carbonitrile (9)

This desired compound 9 (0.072 g, 0.23 mmol) was synthesized with a 77% yield from 0.10 g of 1a (0.30 mmol) and 0.035 g of 2b (0.30 mmol) following a procedure similar to the synthesis of 7. The sample for analysis was recrystallized from DMF to obtain yellow needles, with a melting point of 344–345 °C. 1H NMR (500 MHz, CDCl3) δ: 9.42 (d, J = 7.5 Hz, 1H), 8.05 (d, J = 9.0 Hz, 1H), 8.01 (d, J = 8.0 Hz, 2H), 7.97 (m, 1H), 7.54 (m, 3H), 7.35 (m, 1H), 7.12 (s, 1H). 13C NMR (125 MHz, CDCl3) δ: 162.2, 157.4, 154.1, 149.5, 148.0, 138.9, 132.2, 130.9, 130.6, 129.1, 126.6, 123.3, 117.2, 115.3, 97.4, 96.7, 80.6. MS spectrum (ESI, m/z): 314 [M+]. HRMS (ESI, m/z): Calcd. for C19H10N2O3 [M+]: 314.0691. Found: 314.0691.

3.9. Synthetic Method of 3-(4-methoxyphenyl)-1,11-dioxo-1H,11H-pyrano[4,3-b]quinolizine-5-carbonitrile (10)

This desired compound 10 (0.32 g, 0.93 mmol) was synthesized with a 93% yield from 0.34 g of 1b (1.0 mmol) and 0.12 g of 2b (1.0 mmol) following a procedure similar to the synthesis of 7. The sample for analysis was recrystallized from DMF to obtain yellow needles, with a melting point of 323–324 °C. 1H NMR (500 MHz, CDCl3) δ: 9.38 (d, J = 7.0 Hz, 1H), 8.02 (d, J = 9.0 Hz, 1H), 7.97 (m, 3H), 7.31 (dd, J = 6.5, 7.0 Hz, 1H), 7.03 (s, 1H), 7.00 (d, J = 9.5 Hz, 2H), 3.90 (s, 3H). 13C NMR (125 MHz, CDCl3) δ: 163.0, 162.3, 157.6, 154.1, 149.7, 148.1, 138.7, 130.8, 128.5, 123.2, 122.9, 116.9, 115.4, 114.6, 96.2, 95.7, 80.3, 55.6. MS spectrum (ESI, m/z): 344 [M+]. HRMS (ESI, m/z): Calcd. for C20H12N2O4 [M+]: 344.1797. Found: 344.0799.

3.10. Experimental Procedure of Spectral Measurements

UV/Vis absorption: Each compound was dissolved in DMSO to obtain a stock solution of 10−2 mol/L. Upon measuring, solutions of compounds (10−4 mol/L) were formulated utilizing a measurement solvent before the UV/Vis absorption analysis. After placing the solution in a cuvette and calibrating the UV/Vis spectrometer, the UV/Vis absorption spectra were acquired by scanning from 250 nm to 500 nm. Fluorescence: The slit widths for excitation and emission were set to 5 nm band pass, and the scan speed was set to 1000 nm/min. Each compound was dissolved in DMSO (FUJIFILM Wako Chemicals, Osaka, Japan) to obtain a stock solution of 10−2 mol/L. Upon measuring, a solution of compounds (10−5 mol/L) was formulated utilizing a measurement solvent before the fluorescence analysis. The solution was placed in a quartz cell, set in a fluorescence spectrometer, and the excitation wavelength of the evaluated compound was measured by examining the emission wavelength. Similarly, the emission wavelength was determined by determining the excitation wavelength of the evaluated compounds. By repeating this procedure, the exact excitation and emission wavelengths for each compound were obtained. The quantum yield of fluorescence (Φ) was determined with rhodamine B as a reference (Φ = 0.7 in EtOH).

3.11. Evaluation of the Aggregation Behavior

The aggregation behavior of each compound was evaluated using the dynamic light scattering (DLS) analysis with the Zetasizer Pro (Malvern Panalytical Ltd., Malvern, UK). Samples were diluted in EtOH and water solutions of different ratios, and the particle size was measured. The average of three measurements for each sample was utilized.

3.12. Total ROS Generation Activity Assay

The total ROS generation activity after light exposure to compounds (3–10) was verified using the Cell Meter™ Fluorimetric Intracellular Total ROS Activity Assay Kit Red Fluorescence (AAT Bioquest, Inc., Sunnyvale, CA, USA). The evaluated compounds, initially dissolved in DMSO at 10 mM, subsequently diluted in acetonitrile to an end-point concentration of 200 μM, had 1 μL of Amplite™ ROS RED working solution added. The solution was exposed to LED light (365 nm, 1.7 W, EL-FSE-02-A, Ebisudenshi Co., Ltd., Osaka, Japan) for 120 sec. The control consisted of an acetonitrile solution without any compound. Fluorescence spectra excited at 520 nm were recorded using an FP-8300 spectrometer (JASCO, Tokyo, Japan).

3.13. 1O2 Generation Activity Assay

DPBF was used to confirm the 1O2 generation activity. In a 96-well plate, 10 μL of DPBF in DMSO (10 mM) was blended with 2 μL of compounds 3–10 in DMSO (10 mM). Subsequently, this solution was made up to 100 μL with acetonitrile or a 50:50 (v/v) mixture of acetonitrile and water. After exposure to light (365 nm, 1.7 W, EL-FSE-02-A, Ebisudenshi Co., Ltd., Osaka, Japan) for up to 180 sec, the absorbance data at 405 nm were obtained using a microplate reader (Multiskan FC, Thermo Fisher Scientific, Waltham, MA, USA). The 1O2 quantum yield (ΦΔ) was calculated as the initial observed rate constant (k) of DPBF using the following equation:
ΦΔx = ΦΔ SP · (kx/kSP) · (FSP/Fx)
where SP represents benzophenone, which is utilized as a standard photosensitizer; ΦΔ SP denotes the ΦΔ value of benzophenone (0.39 in acetonitrile); and F signifies the absorption cofactor, expressed as F = 1 − 10OD, where OD represents the optical density at the irradiated wavelength.

3.14. Investigation of In Vitro Anti-Tumor Activity

Human colorectal adenocarcinoma Colo205 cells were cultured in RPMI 1640 media with 10% (v/v) heat-inactivated fetal calf serum, penicillin (100 IU/mL), and streptomycin (100 μg/mL) at 37 °C in a 95% air and 5% CO2 atmosphere. In 96-well plates, Colo205 cells were seeded at a density of 1  × 104 cells/well and cultured for 24 h. Compounds 3–10 (0–30 μM) were then added to the culture medium. After 4 h, the plates were exposed to 365 nm LED light irradiation. Following 48 h of incubation, cytotoxicity and cell viability/growth were assessed using 0.5% (w/v) trypan blue exclusion and 10 μL WST-8 assays. The reductions in the fraction of viable cells were determined using the GloMax Multi Detection System (Promega Corp., Madison, WI, USA) to measure absorbance at 450 nm (reference at 600 nm).

4. Conclusions

To develop new photosensitizers for PDT in cancer treatment, we synthesized 3-phenyl pyrano[4,3-b]quinolizine compounds (3–10) with moderate-to-good yields by reacting pyrones (1a–e) with 2-pyridylacetate (2a) or 2-pyridylacetonitrile (2b). Photophysical analysis showed that all compounds emitted blue-to-green fluorescence with wavelengths ranging from 446 nm to 515 nm in ethanol. Specifically, only compounds 5 and 6, lacking a substituent at position 5 of the pyrano[4,3-b]quinolizine, maintained strong fluorescence as the water content in the solvent increased, indicating AIEE properties. In terms of ROS generation, all compounds produced ROS, particularly 1O2, upon light exposure. Interestingly, compounds 5 and 6, which exhibited AIEE properties, demonstrated significantly increased 1O2 generation in the aggregated state. Furthermore, in assays using Colo205 cells, compounds 5 and 6 showed potent anti-tumor activity following LED light exposure. These findings suggest that 3-phenyl pyrano[4,3-b]quinolizine-based compounds 5 and 6 have the potential to serve as innovative photosensitizers for PDT in cancer treatment. Further evaluations across a wider range of cancer cell lines are planned to validate their efficacy.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/molecules30071422/s1, Figure S1: 1H NMR spectrum (400 MHz, CDCl3) of 3; Figure S2: 13C NMR spectrum (100 MHz, CDCl3) of 3; Figure S3: 1H NMR spectrum (400 MHz, CDCl3) of 4; Figure S4: 13C NMR spectrum (100 MHz, CDCl3) of 4; Figure S5: 1H NMR spectrum (400 MHz, CDCl3) of 5; Figure S6: 13C NMR spectrum (100 MHz, CDCl3) of 5; Figure S7: 1H NMR spectrum (400 MHz, DMSO-d6) of 6; Figure S8: 13C NMR spectrum (100 MHz, DMSO-d6) of 6; Figure S9: 1H NMR spectrum (400 MHz, CDCl3) of 7; Figure S10: 13C NMR spectrum (100 MHz, CDCl3) of 7; Figure S11: 1H NMR spectrum (400 MHz, CDCl3) of 8; Figure S12: 13C NMR spectrum (100 MHz, CDCl3) of 8; Figure S13: 1H NMR spectrum (500 MHz, CDCl3) of 9; Figure S14: 13C NMR spectrum of (125 MHz, CDCl3) 9; Figure S15: 1H NMR spectrum (500 MHz, CDCl3) of 10; Figure S16: 13C NMR spectrum (125 MHz, CDCl3) of 10; Figure S17: UV/Vis spectrum of 3–10 in EtOH; Figure S18: Fluorescence spectrum of 3–10 in EtOH. Figure S19: Anti-tumor activities of 3-phenyl pyrano[4,3-b]quinolizine compounds (3–10) against human colon cancer cells (Colo205) without 365 nm LED light irradiation.

Author Contributions

Conceptualization, M.H. and K.T.; methodology, M.H., T.Y., Y.O., and K.T.; validation, M.H., T.Y., Y.O., and K.T.; formal analysis, M.H., S.T., F.H., and Y.O.; investigation, M.H., T.Y., T.T., S.T., F.H., Y.O., and K.T.; data curation, M.H., T.Y., and Y.O.; writing—original draft preparation, M.H. and Y.O.; writing—review and editing, M.H., T.Y., Y.O., and K.T.; visualization, M.H.; supervision, M.H. and K.T.; project administration, M.H. and K.T. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data presented in this study are available in the article.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Wang, X.; Ding, Q.; Groleau, R.R.; Wu, L.; Mao, Y.; Che., F.; Kotova, O.; Scanlan, E.M.; Lewis, S.E.; Li, P.; et al. Fluorescent Probes for Disease Diagnosis. Chem. Rev. 2024, 124, 7106–7164. [Google Scholar] [CrossRef]
  2. Tao, P.; Miao, Y.; Wang, H.; Xu, B.; Zhao, Q. High-performance organic electroluminescence: Design from organic light-emitting materials to devices. Chem. Rec. 2019, 19, 1531–1561. [Google Scholar] [CrossRef]
  3. Jeon, S.K.; Lee, H.L.; Yook, K.S.; Lee, J.Y. Recent progress of the lifetime of organic light-emitting diodes based on thermally activated delayed fluorescent material. Adv. Mater. 2019, 31, e1803524. [Google Scholar] [CrossRef] [PubMed]
  4. Toseland, C.P. Fluorescent labeling and modification of proteins. J. Chem. Biol. 2013, 6, 85–95. [Google Scholar] [CrossRef] [PubMed]
  5. Boeneman, K.; Delehanty, J.B.; Susumu, K.; Stewart, M.H.; Deschamps, J.R.; Medintz, I.L. Quantum dots and fluorescent protein FRET-based biosensors. Adv. Exp. Med. Biol. 2012, 733, 63–74. [Google Scholar] [PubMed]
  6. Pérez–Gutiérrez, E.; Percino, M.J.; Bernal, Q.W.; Cerón, M.; Ceballos, P.; Rivadeneyra, M.S.; Siegler, M.A.; Thamotharan, S. Fluorescence tuning with a single dye embedded in a polymer matrix and its application on multicolor OLEDs. Dyes Pigm. 2021, 186, 108979. [Google Scholar] [CrossRef]
  7. Zhang, X.; Wang, J.; Liu, Y.; Hao, Y.; Yu, F.; Li, D.; Huang, X.; Yu, L.; Wang, T.; Hao, H. Tunable emission of organic fluorescent crystals through polymorphic manipulation. J. Phys. Chem. C 2021, 125, 6189–6199. [Google Scholar] [CrossRef]
  8. Wang, Z.; Wang, S.; Zhang, Y.; Ma, M. Design, Synthesis, and evaluation of small fluorescent molecules with a 1,1-dimethylnaphthalen-2-(1H)-one core. Molecules 2024, 29, 3396. [Google Scholar] [CrossRef]
  9. Birks, J.B. Photophysics of Aromatic Molecules; Wiley: New York, NY, USA, 1970. [Google Scholar]
  10. Chen, R.F.; Knutson, J.R. Mechanism of fluorescence concentration quenching of carboxyfluorescein in liposomes: Energy transfer to nonfluorescent dimers. Anal. Biochem. 1988, 172, 61–67. [Google Scholar] [CrossRef]
  11. Kathiravan, A.; Sundaravel, K.; Jaccob, M.; Dhinagaran, G.; Rameshkumar, A.; Arul Ananth, D.A.; Sivasudha, T. Pyrene schiff base: Photophysics, aggregation induced emission, and antimicrobial properties. J. Phys. Chem. B 2014, 118, 13573–13581. [Google Scholar] [CrossRef]
  12. Gopikrishna, P.; Meher, N.; Iyer, P.K. Functional 1,8-naphthalimide AIE/AIEEgens: Recent advances and prospects. ACS Appl. Mater. Interfaces 2018, 10, 12081–12111. [Google Scholar] [CrossRef]
  13. Hagimori, M.; Yoshida, T.; Nishimura, Y.; Ogawa, Y.; Tanaka, K. Syntheses of novel pyridine-based low-molecular-weight luminogens possessing aggregation-induced emission enhancement (AIEE) properties. Beilstein J. Org. Chem. 2022, 18, 580–587. [Google Scholar] [CrossRef]
  14. Bray, F.; Laversanne, M.; Sung, H.; Ferlay, J.; Siegel, R.L.; Soerjomataram, I.; Jemal, A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2024, 74, 229–263. [Google Scholar] [CrossRef]
  15. Liu, B.; Zhou, H.; Tan, L.; Siu, K.T.H.; Guan, X.Y. Exploring treatment options in cancer: Tumor treatment strategies. Signal Transduct. Target Ther. 2024, 9, 175. [Google Scholar] [CrossRef] [PubMed]
  16. Garcia-Diaz, M.; Huang, Y.Y.; Hamblin, M.R. Use of fluorescent probes for ROS to tease apart Type I and Type II photochemical pathways in photodynamic therapy. Methods 2016, 109, 158–166. [Google Scholar] [CrossRef]
  17. Alzeibak, R.; Mishchenko, T.A.; Shilyagina, N.Y.; Balalaeva, I.V.; Vedunova, M.V.; Krysko, D.V. Targeting immunogenic cancer cell death by photodynamic therapy: Past, present and future. J. Immunother. Cancer 2021, 9, e001926. [Google Scholar] [CrossRef] [PubMed]
  18. Akbar, A.; Khan, S.; Chatterjee, T.; Ghosh, M. Unleashing the power of porphyrin photosensitizers: Illuminating breakthroughs in photodynamic therapy. J. Photochem. Photobiol. B 2023, 248, 112796. [Google Scholar] [CrossRef]
  19. Nanashima, A.; Abo, T.; Nonaka, T.; Nonaka, Y.; Morisaki, T.; Uehara, R.; Ohnita, K.; Fukuda, D.; Murakami, G.; Tou, K.; et al. Photodynamic therapy using talaporfin sodium (Laserphyrin®) for bile duct carcinoma: A preliminary clinical trial. Anticancer Res. 2012, 32, 4931–4938. [Google Scholar] [CrossRef] [PubMed]
  20. Gomes-da-Silva, L.C.; Zhao, L.; Bezu, L.; Zhou, H.; Sauvat, A.; Liu, P.; Durand, S.; Leduc, M.; Souquere, S.; Loos, F.; et al. Photodynamic therapy with redaporfin targets the endoplasmic reticulum and Golgi apparatus. EMBO J. 2018, 37, e98354. [Google Scholar] [CrossRef]
  21. Dadwal, S.; Deol, H.; Kumar, M.; Bhalla, V. AIEE Active nanoassemblies of pyrazine based organic photosensitizers as efficient metal-free supramolecular photoredox catalytic systems. Sci. Rep. 2019, 9, 11142. [Google Scholar] [CrossRef]
  22. Chen, J.W.; Chang, C.C. A dual anticancer efficacy molecule: A selective dark cytotoxicity photosensitizer. ACS Appl. Mater. Interfaces 2016, 8, 29883–29892. [Google Scholar] [PubMed]
  23. Yu, Z.X.; Meng, X.X.; Zhang, S.N.; Wang, X.D.; Chen, Y.S.; Min, P.R.; Zhang, Z.; Zhang, Y. IR-808 loaded nanoethosomes for aggregation-enhanced synergistic transdermal photodynamic/photothermal treatment of hypertrophic scars. Biomaterials Sci. 2021, 10, 158–166. [Google Scholar] [CrossRef]
  24. Hagimori, M.; Mizuyama, N.; Tominaga, Y. Synthesis of pyrano[4,3-b]quinolizine derivatives from 6-aryl or styryl-4-methylsulfanyl-2-oxo-2H-pyrans and their fluorescence. ARKIVOC 2008, 13, 16–27. [Google Scholar]
  25. Hara, F.; Mizuyama, N.; Fujino, T.; Takada, S.; Temma, T.; Saji, H.; Mukai, T.; Hagimori, M. Development of a pyrone-fused tricyclic scaffold-based ratiometric fluorescent probe for Al3+ detection. J. Fluores. 2024, in press. [Google Scholar]
  26. Santos, E.M.; Sheng, W.; Salmani, R.E.; Nick, S.T.; Ghanbarpour, A.; Gholami, H.; Vasileiou, C.; Geiger, J.H.; Borhan, B. Design of large stokes shift fluorescent proteins based on excited state proton transfer of an engineered photobase. J. Am. Chem. Soc. 2021, 143, 15091–15102. [Google Scholar]
  27. Zou, L.; Wang, R.; Zhao, M.; Li, Y.; Sun, C.; Xie, J.; Chen, Y.; Jing, Q.; Mi, D.; Shi, S. PLGA confers upon conventional nonfluorescent molecules luminescent properties to trigger 1O2-induced pyroptosis and immune response in tumors. J. Nanobiotechnol. 2025, 23, 35. [Google Scholar]
Molecules 30 01422 sch001
Scheme 1. Syntheses of 3-phenylpyrano[4,3-b]quinolizine compounds (3–10).
Scheme 1. Syntheses of 3-phenylpyrano[4,3-b]quinolizine compounds (3–10).
Molecules 30 01422 sch001
Molecules 30 01422 g001
Figure 1. Fluorescence spectra of (a) 3 (10−5 M, λex = 435 nm); (b) 4 (10−5 M, λex = 438 nm); (c) 5 (10−5 M, λex = 441 nm); (d) 6 (10−5 M, λex = 445 nm); (e) 7 (10−5 M, λex = 366 nm); (f) 8 (10−5 M, λex = 368 nm) ); (g) 9 (10−5 M, λex = 432 nm); (h) 10 (10−5 M, λex = 434 nm) in H2O/ethanol mixture with different water fractions. Insets show the fluorescence intensity at each Emmax. The arrows indicate the decrease in fluorescence with increasing water ratio.
Figure 1. Fluorescence spectra of (a) 3 (10−5 M, λex = 435 nm); (b) 4 (10−5 M, λex = 438 nm); (c) 5 (10−5 M, λex = 441 nm); (d) 6 (10−5 M, λex = 445 nm); (e) 7 (10−5 M, λex = 366 nm); (f) 8 (10−5 M, λex = 368 nm) ); (g) 9 (10−5 M, λex = 432 nm); (h) 10 (10−5 M, λex = 434 nm) in H2O/ethanol mixture with different water fractions. Insets show the fluorescence intensity at each Emmax. The arrows indicate the decrease in fluorescence with increasing water ratio.
Molecules 30 01422 g001
Molecules 30 01422 g002
Figure 2. Relative ROS generation of acetonitrile solutions of 3–10 under 365 nm irradiation.
Figure 2. Relative ROS generation of acetonitrile solutions of 3–10 under 365 nm irradiation.
Molecules 30 01422 g002
Molecules 30 01422 g003
Figure 3. Change in absorbance of DPBF at 405 nm during the photodecomposition of DPBF by 1O2 in the presence of compounds 3–10 (2 × 10−4 M) upon irradiation at 365 nm. (a) 3; (b) 4; (c) 5; (d) 6; (e) 7; (f) 8; (g) 9; (h) 10 in CH3CN (solid line) and CH3CN-H2O (50%, v/v) (dot line).
Figure 3. Change in absorbance of DPBF at 405 nm during the photodecomposition of DPBF by 1O2 in the presence of compounds 3–10 (2 × 10−4 M) upon irradiation at 365 nm. (a) 3; (b) 4; (c) 5; (d) 6; (e) 7; (f) 8; (g) 9; (h) 10 in CH3CN (solid line) and CH3CN-H2O (50%, v/v) (dot line).
Molecules 30 01422 g003
Molecules 30 01422 g004
Figure 4. Anti-tumor activities of 3-phenyl pyrano[4,3-b]quinolizine compounds (3–10) against human colon cancer cells (Colo205) after 365 nm LED light irradiation.
Figure 4. Anti-tumor activities of 3-phenyl pyrano[4,3-b]quinolizine compounds (3–10) against human colon cancer cells (Colo205) after 365 nm LED light irradiation.
Molecules 30 01422 g004
Table 1. Fluorescence data for 3–10 in EtOH.
Table 1. Fluorescence data for 3–10 in EtOH.
Compoundsλmax
(nm)		log εEmmax
(nm)		SS [a]ΦFL [b]
34354.15451160.18
44383.97515770.21
54413.97455140.11
64454.36459140.03
73663.165151490.20
83683.884971290.21
94324.01446140.21
104344.23453190.28
[a] Each emission was measured using excitation wavelengths. [b] Fluorescence quantum yields were determined by using rhodamine B as a reference.
Table 2. Particle size of 3–10 in EtOH–water mixture.
Table 2. Particle size of 3–10 in EtOH–water mixture.
Water Fraction (vol%)
030508095
32.0 ± 1.21.1 ± 0.657.0 ± 97.0543.5 ± 377.9460.3 ± 235.5
425.7 ± 44.572.5 ± 121.2263.6 ± 37.4306.4 ± 245.5383.9 ± 354.4
50.7 ± 0.0 0.7 ± 0.1 24.1 ± 40.1 29.8 ± 46.2 265.3 ± 45.5
60.0 ± 0.00.9 ± 0.2235.6 ± 0.1296.9 ± 257.7248.2 ± 73.6
718.8 ± 13.9 8.4 ± 12.3 227.1 ± 38.6 460.0 ± 330.9 76.4 ± 23.0
822.2 ± 38.524.8 ± 37.224.4 ± 36.7375.1 ± 525.6291.4 ± 61.4
917.6 ± 30.4426.4 ± 344.4508.5 ± 223.7585.2 ± 19.1589.4 ± 195.5
1022.6 ± 36.1354.9 ± 95.5 802.4 ± 222.0990.6 ± 176.1411.9 ± 179.2
Average ± S.D. (nm).
Table 3. Observed rate constant and singlet oxygen quantum yields of 3–10 in acetonitrile.
Table 3. Observed rate constant and singlet oxygen quantum yields of 3–10 in acetonitrile.
Compounds Observed Rate Constant
(k) [min−1]		ΦΔ [a]
31.010.91
40.950.85
50.590.53
60.750.67
70.840.75
80.920.83
90.820.73
100.810.72
[a] Singlet oxygen quantum yields were determined by using benzofuran as a reference.
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Hagimori, M.; Yoshida, T.; Tsutsumi, T.; Hara, F.; Takada, S.; Ogawa, Y.; Tanaka, K. Aggregation-Induced Luminescent 3-Phenylpyrano[4,3-b]quinolizine Derivatives as Photosensitizers with Anti-Cancer Properties. Molecules 2025, 30, 1422. https://doi.org/10.3390/molecules30071422

AMA Style

Hagimori M, Yoshida T, Tsutsumi T, Hara F, Takada S, Ogawa Y, Tanaka K. Aggregation-Induced Luminescent 3-Phenylpyrano[4,3-b]quinolizine Derivatives as Photosensitizers with Anti-Cancer Properties. Molecules. 2025; 30(7):1422. https://doi.org/10.3390/molecules30071422

Chicago/Turabian Style

Hagimori, Masayori, Tatsusada Yoshida, Takuma Tsutsumi, Fumiko Hara, Shinya Takada, Yukiko Ogawa, and Keitaro Tanaka. 2025. "Aggregation-Induced Luminescent 3-Phenylpyrano[4,3-b]quinolizine Derivatives as Photosensitizers with Anti-Cancer Properties" Molecules 30, no. 7: 1422. https://doi.org/10.3390/molecules30071422

APA Style

Hagimori, M., Yoshida, T., Tsutsumi, T., Hara, F., Takada, S., Ogawa, Y., & Tanaka, K. (2025). Aggregation-Induced Luminescent 3-Phenylpyrano[4,3-b]quinolizine Derivatives as Photosensitizers with Anti-Cancer Properties. Molecules, 30(7), 1422. https://doi.org/10.3390/molecules30071422

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