Quinoline Derivatives with Different Functional Groups: Evaluation of Their Catecholase Activity

Abstract

In this work, we are interested in finding new catalysts for catecholase, whose principle is based on the oxidation reaction of catechol to o-quinone. In this context, we have studied a series of seven quinoline-based compounds. The present work indicates that the complexes formed between seven selected quinoline compounds and the copper salts viz. Cu(OAc)₂, CuSO₄, Cu(NO₃)₂, and CuCl₂ elicit catalytic activities for the oxidation of catechol to o-quinone. The complexes formed with the Cu(OAc)₂ salt show a much higher catalytic activity than the others, whereas the Cu(NO₃)₂ and CuCl₂ salts formed complexes with low catalytic activity. This study also shows that the oxidation rate depends on two factors, namely the chemical structure of the ligands and the nature of the ions coordinated with the copper.

1. Introduction

Copper is among the important metals in many catalytic processes and is characterized by its ability to combine with organic ligands to catalyze several diverse biological processes [1]. For example, catechol oxidase is a copper-based moiety that catalyzes the oxidation of phenols to quinones in the presence of oxygen. It is found for example in plants, wherein it plays an essential role in catalyzing the oxidation of catechol to o-quinone to produce after polymerization melanin, which gives a dark brown color to damaged fruits [2]. Dopamine is an important neurotransmitter, which after oxidation and polymerization gives polydopamine, an adhesive agent with many industrial applications. The oxidation of phenols to corresponding quinones is a very interesting process that has various applications in many fields [3].

Quinoline derivatives are among the compounds with great pharmacological powers [4], such as antimicrobial [5], anticancer [6,7,8], antifungal [9,10], antiviral [11], anti-inflammatory [12], antioxidants [13,14], antitumor [15], anti-SARS-CoV-2 [16], corrosion inhibitors [17,18], and antimalarial [19]. On the other hand, copper–quinoline complexes are similar systems that can catalyze many biological processes. For this reason, we are interested in this work to better understand this compelling mechanism and to discover the efficiency of quinoline derivatives in the oxidation of catechol.

This work aims to study the effect of ligands–copper(II) complexes on the oxidation of catechol to o-quinone in the presence of O₂ (Scheme 1). In this respect, the reaction was first performed without catalysts, then using the copper salts Cu(OAc)₂, CuSO₄, Cu(NO₃)_2, and CuCl₂, then using the synthesized ligands (L₁, L₂, L₃, L₄, L₅, L₆, and L₇—Scheme 2), and finally, the reaction was catalyzed by the ligands–copper (II) complexes. In order to be able to compare and discuss the obtained results, the oxidation rate for each catechol transformation was calculated.

2. Results and Discussions

The results of this study are represented in Figure 1 and Figure 2, which give the absorbance as a function of time for the different cases. Figure 1a presents the oxidation of catechol without any catalyst, while Figure 1b represents the reaction catalyzed by the synthesized ligands. In Figure 1c, the reaction is catalyzed by the metal salts and finally, Figure 2 provides the obtained results using the complexes formed between the synthesized ligands and the metal salts. Table 1 represents the oxidation rate for the different cases.

We notice from Figure 1a that the absorbance remains at almost zero over time and the oxidation rate is very low viz. 2.78 μmol L⁻¹ s⁻¹. Figure 1b also shows a very low absorbance and conversion rate between 7.08 μmol L⁻¹ s⁻¹ and 12.64 μmol L⁻¹ s⁻¹. From Figure 1c, we also notice that the absorbance and oxidation rate remain low for the metal salts CuSO₄, Cu(NO₃)₂, and CuCl₂; however, the salt Cu(OAc)₂ has a better oxidation rate of 47.22 μmol L⁻¹ s⁻¹. Therefore, it can be deduced that the oxidation reaction cannot take place without a catalyst and that neither ligands nor salts alone can catalyze this reaction, except Cu(OAc)₂, which has a slightly greater catalytic effect compared to the others.

The results obtained in Figure 2 show that the complexes formed between the Cu(OAc)₂ salt and the ligands possess better catalytic activity for the oxidation of catechol, as the obtained oxidation rates are the highest (Figure 2a). The L₄/Cu(OAc)₂ complex shows an oxidation rate of 126.80 μmol L⁻¹ s⁻¹, followed by the L₅/Cu(OAc)₂ complex (114.44 μmol L⁻¹ s⁻¹), then the L₂/Cu(OAc)₂, L₇/Cu(OAc)₂, and L₃/Cu(OAc)₂ complexes with oxidation rates of 94.30, 89.58, and 85.27 μmol L⁻¹ s⁻¹, respectively, and finally, L₁/Cu(OAc)₂ and L₆/Cu(OAc)₂, which give the lowest oxidation rates (71.38 and 69.30 μmol L⁻¹ s⁻¹, respectively).

The complexes formed between the ligands and the CuSO₄ salt also give high oxidation rates but are generally lower than those obtained in the case of Cu(OAc)₂, as the highest oxidation rate is 65.13 μmol L⁻¹ s⁻¹ for L₄/CuSO₄, followed by L₅/CuSO₄ and L₇/CuSO₄, with oxidation rates of 52.63 and 48.75 μmol L⁻¹ s⁻¹, respectively, and then the complexes formed between CuSO₄ and ligands L₁, L₃, L₆, and L₂ come last with oxidation rates of 34.86, 27.91, 26.53, and 26.25 μmol L⁻¹ s⁻¹, respectively (Figure 2b).

The complexes formed between the ligands and Cu(NO₃)₂ also catalyze the oxidation reaction, but with slightly lower oxidation rates compared to the previous ones, as the L₃/Cu(NO₃)₂ complex gives the largest oxidation rate of 31.25 μmol L⁻¹ s⁻¹, followed by the L₅/Cu(NO₃)₂ complex (27.64 μmol L⁻¹ s⁻¹), and then the complexes formed between Cu(NO₃)₂ and the ligands L₂, L₇, L₃, L₁, and L₆, with oxidation rates of 18.61, 17.91, 17.36, 16.53, and 14.03 μmol L⁻¹ s⁻¹, respectively (Figure 2c).

The complexes formed between the ligands and CuCl₂ do not show a significant catalytic effect, as there is no significant increase in absorbance in all cases, and the oxidation rate remains quite low, the largest conversion rate being 15.55 μmol L⁻¹ s⁻¹ for L₄/CuCl₂ and the smallest being 11.25 μmol L⁻¹ s⁻¹ for L₂/CuCl₂ (Figure 2d). We deduce from these results that the chemical structure of the ligands and the nature of the copper salts play an important role in the catalytic activity of the studied complexes.

It can be seen from this study that all the complexes formed between the ligands and Cu(OAc)₂ have very high catalytic activities compared to the complexes formed with the other salts, and this is due to the weak bonding between the OAc⁻ anions and the Cu²⁺ cations, which facilitates the coordination between the ligands and copper. On the other hand, the ligands L₄ and L₅ form complexes with a very high catalytic activity, because the presence of electron donor groups increases the electron density at the nitrogen atom, which favors the coordination with the metal and the formation of stable complexes. However, in the case of L₁ and L₆, the catalytic activity decreases due to the presence of electron-withdrawing groups (Cl and CO) that weaken the electron density at the oxygen atom and thus disfavor the formation of the copper–metal bond. In the case of complexes formed between the ligands and the metal salt CuCl₂, the absorbance remains low, and the catalytic activity decreases because the Cl^- anions are strongly bound to copper, and the coordination between the metal and the ligands thus becomes very difficult.

In summary, the catalytic activity of copper salts and quinoline ligands is very low, but their assembly results in complexes that efficiently catalyze the oxidation of catechol to o-quinone. The results show that the oxidation rate depends on two factors, namely the ions’ nature, and the ligands’ chemical structure. The ions strongly bound to copper reduce the coordination of the ligands, resulting in complexes of low catalytic activity, and the reverse is true for the ions weakly bound to copper, which facilitate the coordination of the ligands, giving stable complexes and high catalytic activities. On the other hand, the chemical structure of the ligands plays an essential role, and the presence of electron-donating groups enriches the coordination site in electron density, which increases the stability of the studied complex as well as its catalytic activity. However, the presence of electron-withdrawing groups decreases the electron density at the coordination site, which decreases the stability of the complex and its catalytic activity.

3. Materials and Methods

3.1. Reaction and Method

The reaction studied is schematized in Scheme 1, the kinetics of this reaction was followed by measuring the absorbance as a function of time by a UV–Vis spectrophotometer for one hour at 390 nm (absorption maximum of o-quinone), under the following conditions: T = 25 °C, ε = 1.6 L mol⁻¹ cm⁻¹. The solutions are prepared by dissolving in methanol, and the complexes are synthesized in situ by mixing 0.15 mL of a solution (2 × 10⁻³ mol L⁻¹) of CuX₂, nH₂O, and 0.15 mL of a solution (2 × 10⁻³ mol L⁻¹) of the ligand, and then 2 mL of a solution of catechol at a concentration of 10⁻¹ mol L⁻¹ is added [20].

3.2. Synthesis of Ligands

The studied quinoline derivatives were synthesized according to the procedures described in the literature (Scheme 3):

Synthesis of 2-chloroquinoline-3-carbaldehyde (compound L₁): DMF (3 eq) and POCl₃ (4.5 eq) were stirred for 30 min at 0 °C, then acetanilide (1 eq) in CHCl₃ (15 mL) was added slowly, and after the addition, the reaction mixture was heated for 16 h (80–90 °C). When the reaction was complete, the mixture was poured into crushed ice and neutralized with saturated NaHCO₃ solution; the resulting precipitate was filtered, washed with water, and recrystallized in ethyl acetate [21].

Synthesis of 2-chloroquinoline-3-carboxylic acid (compound L₂): 89 mg of compound L₁ were dissolved in a minimum of ethanol, then an ethanolic solution of AgNO₃ (0.7 mmol) and NaOH (2.5 mmol) were added. The mixture was left under stirring at room temperature for 4 h; at the end of the reaction, the excess AgNO₃ was removed by filtration, then a few drops of concentrated sulfuric acid were added to neutralize the solution. The precipitate formed was filtered, washed with water, and dried to give a dark yellow product [22].

Synthesis of ethyl 2-chloroquinoline-3-carboxylate (compound L₃): In a minimum of ethanol, 100 mg of compound L₂ and 4 drops of concentrated sulfuric acid were added, and the mixture was refluxed for 8 h. After cooling, the solid formed was recovered by filtration, washed with water, dried, and recrystallized in ethanol [23].

Synthesis of 2-chloroquinoline-3-carbohydrazide (compound L₄): 0.5 mmol of compound L₃ and 0.5 mmol of hydrazine were heated at reflux for 4 h in a minimum of ethanol, and at the end of the reaction, 50 g of ice was added to the solution and the obtained precipitate was filtered, washed with water, dried, and recrystallized in ethanol [24].

Synthesis of N′-benzylidene-2-chloroquinoline-3-carbohydrazide (compound L₅): To 15 mL of ethanol, 56 mg of compound L₄ and 40 mg of benzaldehyde and a few drops of acetic acid were added and heated at reflux for 12 h. At the end of the reaction, the reaction mixture was allowed to reach room temperature and the resulting precipitate was filtered, washed with water, dried, and recrystallized in ethanol [25].

Synthesis of 2-oxo-1,2-dihydroquinoline-3-carbaldehyde (compound L₆): Compound L₁ (1 mmol) was heated to 110 °C for 12 h in acetic acid (70%), and at the end of the reaction, the reaction mixture was allowed to reach room temperature. The precipitate formed was filtered and washed with water, dried, and recrystallized in ethanol [26].

Synthesis of 3-(2-chloroquinolin-3-yl)-1-phenylprop-2-en-1-one (compound L₇): To 20 mL of ethanol, 1 mmol of acetophenone, 1 mmol of compound L₁, and 5 mL of 10% NaOH solution were added. After 8 h of stirring at room temperature, the precipitate formed was filtered, washed with water, and recrystallized in ethanol [27].

NMR data of all these ligands are available in the file Supplementary Materials.

4. Conclusions

The results of this study show that the studied quinoline-derived complexes possess catalytic activities, and in particular, the complexes formed between the ligands and the metal salt Cu(OAc)₂ efficiently catalyze the oxidation of catechol to o-quinone. The 2-chloroquinoline-3-carbohydrazide ligand (compound L₄) exhibits the highest catalytic activity, and 2-oxo-1,2-dihydroquinoline-3-carbaldehyde (compound L₆) exhibits the lowest catalytic activity. In general, the oxidation efficiency of the studied complexes depends on the ions’ nature and the ligands’ chemical structure. Ions weakly bound to the metal and electron-rich coordination sites yield stable complexes that strongly catalyze catechol oxidation. Further studies are still in progress in our laboratory to synthesize new quinoline derivatives, evaluate their biological and catalytic activities, as well as to obtain more details on this compelling catalytic process.

Author Contributions

R.S. and S.T.: conceptualization, supervision, project administration, methodology, resources, data curation, writing of the original draft, review, and editing; M.M.: conduct of experiment; V.H.M.: review and editing, methodology; J.J.: project administration; Z.M.A., M.I.A.-Z. and A.B.B.: project administration, methodology, writing of original draft and paying publication fees. All authors have read and agreed to the published version of the manuscript.

Data Availability Statement

The data presented in this study are available on request from the corresponding author.

Acknowledgments

The authors extend their appreciation to the Deanship of Scientific Research at King Saud University for funding this work through research group No (RGP-070).

Conflicts of Interest

The authors declare no conflict of interest.

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures, Schemes and Table

Scheme 1. The oxidation reaction of catechol to o-quinone.

Scheme 2. Chemical structure of the studied quinoline ligands.

Figure 1. Oxidation of catechol to o-quinone in the absence of copper complexes: (a) Reaction without any catalyst, (b) reaction catalyzed by the synthesized ligands, and (c) reaction synthesized by the metal salts. Reaction conditions: methanol solutions, 0.15 mL metal salt at 2 × 10−3 mol/L, 0.15 mL ligand at 2 × 10−3 mol/L, 2 mL catechol at 10−1 mol/L are mixed, T = 25 °C, λ = 390 nm.

Figure 2. Oxidation of catechol to o-quinone in the presence of copper complexes: (a) Reaction in the presence of Cu(OAc)2 and ligands, (b) reaction in the presence of CuSO4 and ligands, (c) reaction in the presence of Cu(NO)3 and ligands, and (d) reaction in the presence of CuCl2 and ligands. Reaction conditions: methanol solutions, 0.15 mL metal salt at 2 × 10−3 mol/L, 0.15 mL ligand at 2 × 10−3 mol/L, 2 mL catechol at 10−1 mol/L are mixed, T = 25 °C, λ = 390 nm.

Scheme 3. Protocol for the synthesis of quinoline derivatives.

Table 1

Oxidation rate of catechol to o-quinone in (μmol L⁻¹ s⁻¹).

	Cu(OAc)2	CuSO4	Cu(NO3)2	CuCl2	Ligands Only
L1	71.38	34.86	16.53	13.33	11.39
L2	94.30	26.25	18.61	11.25	10.83
L3	85.27	27.91	17.36	12.22	12.08
L4	126.80	65.13	31.25	15.55	12.64
L5	114.44	52.63	27.64	14.03	8.61
L6	69.30	26.53	14.03	11.39	7.92
L7	89.58	48.75	17.91	12.64	7.08
Salt only	47.63	17.91	13.33	5.83
Without catalysis	2.78

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/catal12111468/s1.

References

1. Trammell, R.; Rajabimoghadam, K.; Garcia-Bosch, I. Copper-promoted functionalization of organic molecules: From biologically relevant Cu/O₂ model systems to organometallic transformations. Chem. Rev.; 2019; 119, pp. 2954-3031. [DOI: https://dx.doi.org/10.1021/acs.chemrev.8b00368] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30698952]

2. Tripathy, R.; Singha, S.; Sarkar, S. A review on bio-functional models of catechol oxidase probed by less explored first-row transition metals. J. Coord. Chem.; 2022; 8, pp. 1-51. [DOI: https://dx.doi.org/10.1080/00958972.2022.2122053]

3. Hauser, D.; Septiadi, D.; Turner, J.; Petri-Fink, A.; Rothen-Rutishauser, B. From bioinspired glue to medicine: Polydopamine as a biomedical material. Materials; 2020; 13, 1730. [DOI: https://dx.doi.org/10.3390/ma13071730] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32272786]

4. Tabassum, R.; Ashfaq, M.; Oku, H. Current pharmaceutical aspects of synthetic quinoline derivatives. Mini-Rev. Med. Chem.; 2021; 21, pp. 1152-1172. [DOI: https://dx.doi.org/10.2174/1389557520999201214234735] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/33319670]

5. Insuasty, D.; Vidal, O.; Bernal, A.; Marquez, E.; Guzman, J. Antimicrobial activity of quinoline-based hydroxyimidazolium hybrids. Antibiotics; 2019; 8, 239. [DOI: https://dx.doi.org/10.3390/antibiotics8040239]

6. Guan, Y.F.; Liu, X.J.; Yuan, X.Y.; Liu, W.B.; Li, Y.R.; Yu, G.X.; Zhang, S.Y. Design, Synthesis, and Anticancer Activity Studies of Novel Quinoline-Chalcone Derivatives. Molecules; 2021; 26, 4899. [DOI: https://dx.doi.org/10.3390/molecules26164899]

7. Diaconu, D.; Antoci, V.; Mangalagiu, V.; Amariucai-Mantu, D.; Mangalagiu, I.I. Quinoline–imidazole/benzimidazole derivatives as dual-/multi-targeting hybrids inhibitors with anticancer and antimicrobial activity. Sci. Rep.; 2022; 12, pp. 1-17. [DOI: https://dx.doi.org/10.1038/s41598-022-21435-6]

8. Zablotsky, D.; Segal, I.; Zablotskaya, A.; Maiorov, M.; Nguyen, T.A. 19—Antimicrobial Activity of Hybrid Organic-Inorganic Core-Shell Magnetic Nanocomposites. Magnetic Nanoparticle-Based Hybrid Materials; Woodhead Publishing: Cambridge, UK, 2021; pp. 501-507. [DOI: https://dx.doi.org/10.1016/b978-0-12-823688-8.00013-2] ISBN 978-0-12-823688-8

9. Ajani, O.O.; Iyaye, K.T.; Ademosun, O.T. Recent advances in chemistry and therapeutic potential of functionalized quinoline motifs–A review. RSC Adv.; 2022; 12, pp. 18594-18614. [DOI: https://dx.doi.org/10.1039/D2RA02896D]

10. Qin, T.H.; Liu, J.C.; Zhang, J.Y.; Tang, L.X.; Ma, Y.N.; Yang, R. Synthesis and biological evaluation of new 2-substituted-4-amino-quinolines and-quinazoline as potential antifungal agents. Bioorganic Med. Chem. Lett.; 2022; 72, 128877. [DOI: https://dx.doi.org/10.1016/j.bmcl.2022.128877]

11. Wyman, K.A.; Girgis, A.S.; Surapaneni, P.S.; Moore, J.M.; Abo Shama, N.M.; Mahmoud, S.H.; Panda, S.S. Synthesis of Potential Antiviral Agents for SARS-CoV-2 Using Molecular Hybridization Approach. Molecules; 2022; 27, 5923. [DOI: https://dx.doi.org/10.3390/molecules27185923]

12. Ji, K.L.; Liu, W.; Yin, W.H.; Li, J.Y.; Yue, J.M. Quinoline alkaloids with anti-inflammatory activity from Zanthoxylum avicennae. Org. Biomol. Chem.; 2022; 20, pp. 4176-4182. [DOI: https://dx.doi.org/10.1039/D2OB00711H] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/35535577]

13. Abdi, B.; Fekadu, M.; Zeleke, D.; Eswaramoorthy, R.; Melaku, Y. Synthesis and Evaluation of the Antibacterial and Antioxidant Activities of Some Novel Chloroquinoline Analogs. J. Chem.; 2021; 2021, 2408006. [DOI: https://dx.doi.org/10.1155/2021/2408006]

14. El-Saghier, A.M.; El-Naggar, M.; Husseinm, A.H.M.; El-Adasy, A.B.A.; Olish, M.; Abdelmonsef, A.H. Eco-Friendly Synthesis, Biological Evaluation, and In Silico Molecular Docking Approach of Some New Quinoline Derivatives as Potential Antioxidant and Antibacterial Agents. Front. Chem.; 2021; 397, 679967. [DOI: https://dx.doi.org/10.3389/fchem.2021.679967] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/34178944]

15. El Rhabori, S.; El Aissouq, A.; Chtita, S.; Khalil, F. Design of novel quinoline derivatives as anti-breast cancer using 3D-QSAR, molecular docking, and pharmacokinetic investigation. Anti-Cancer Drugs; 2022; 33, pp. 789-802. [DOI: https://dx.doi.org/10.1097/CAD.0000000000001318] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/36136985]

16. Gentile, D.; Fuochi, V.; Rescifina, A.; Furneri, P.M. New Anti SARS-CoV-2 Targets for Quinoline Derivatives Chloroquine and Hydroxychloroquine. Int. J. Mol. Sci.; 2020; 21, 5856. [DOI: https://dx.doi.org/10.3390/ijms21165856]

17. Verma, C.; Quraishi, M.A.; Ebenso, E.E. Quinoline and its derivatives as corrosion inhibitors: A review. Surf. Interfaces; 2020; 21, 100634. [DOI: https://dx.doi.org/10.1016/j.surfin.2020.100634]

18. Alamiery, A. Investigations on corrosion inhibitory effect of newly quinoline derivative on mild steel in HCl solution complemented with antibacterial studies. Biointerface Res. Appl. Chem.; 2022; 2, pp. 1561-1568.

19. Da Silva Neto, G.J.; Silva, L.R.; Annunciato, Y. Dual quinoline-hybrid compounds with antimalarial activity against Plasmodium falciparum parasites. New J. Chem.; 2022; 46, pp. 6502-6518. [DOI: https://dx.doi.org/10.1039/D1NJ05598D]

20. Saddik, R.; Abrigach, F.; Benchat, N.; El Kadiri, S.; Hammouti, B.; Touzani, R. Catecholase Activity Investigation for Pyridazinone- and Thiopyridazinone-Based Ligands. Res. Chem. Intermed.; 2012; 38, pp. 1987-1998. [DOI: https://dx.doi.org/10.1007/s11164-012-0520-2]

21. Belferdi, F.; Merabet, N.; Belkhiri, L.; Douara, B. Regioselective demethylation of quinoline derivatives. A DFT rationalization. J. Mol. Struct.; 2016; 1118, pp. 10-17. [DOI: https://dx.doi.org/10.1016/j.molstruc.2016.03.034]

22. Syniugin, A.R.; Chekanov, M.O.; Volynets, G.P.; Starosyla, S.A.; Bdzhola, V.G.; Yarmoluk, S.M. Design, synthesis, and evaluation of 3-quinoline carboxylic acids as new inhibitors of protein kinase CK2. J. Enzym. Inhib. Med. Chem.; 2016; 31, pp. 160-169. [DOI: https://dx.doi.org/10.1080/14756366.2016.1222584] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27590574]

23. Krishnakumar, V.; Khan, F.-R.N.; Mandal, B.K.; Mitta, S.; Dhasamandha, R.; Govindan, V.N. Quinoline-3-Carboxylates as Potential Antibacterial Agents. Res. Chem. Intermed.; 2012; 38, pp. 1819-1826. [DOI: https://dx.doi.org/10.1007/s11164-012-0505-1]

24. Abass, M.; Alzandi, A.R.A.; Hassan, M.M.; Mohamed, N. Recent Advances on Diversity Oriented Heterocycle Synthesis of Fused Quinolines and Its Biological Evaluation. Polycycl. Aromat. Compd.; 2021; 41, pp. 2120-2209. [DOI: https://dx.doi.org/10.1080/10406638.2019.1710856]

25. As, T.; Sal, S. Synthesis and Characterisation of Substituted Quinoline by Vilsmeier-Haack Reagent. Int. J. Chem. Stud.; 2017; 5, pp. 1-4.

26. Hamama, W.S.; Ibrahim, M.E.; Gooda, A.A.; Zoorob, H.H. Recent Advances in the Chemistry of 2-Chloroquinoline-3-Carbaldehyde and Related Analogs. RSC Adv.; 2018; 8, pp. 8484-8515. [DOI: https://dx.doi.org/10.1039/C7RA11537G] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/35539824]

27. Li, W.; Xu, F.; Shuai, W.; Sun, H.; Yao, H.; Ma, C.; Xu, S.; Yao, H.; Zhu, Z.; Yang, D.-H. et al. Discovery of Novel Quinoline–Chalcone Derivatives as Potent Antitumor Agents with Microtubule Polymerization Inhibitory Activity. J. Med. Chem.; 2019; 62, pp. 993-1013. [DOI: https://dx.doi.org/10.1021/acs.jmedchem.8b01755]