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Clinical Cancer Investigation Journal
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Year: 2022   |   Volume: 11   |   Issue: 6   |   Page: 16-20     View issue

Evaluation of Interaction of Some Quinolone Derivatives on RSK-4 Using a Theoretical Model

 

Marcela Rosas-Nexticapa1, Lauro Figueroa-Valverde2*, Magdalena Alvarez-Ramirez1, Maria Lopez-Ramos2, Virginia Mateu-Armand1*, Tomas Lopez-Gutierrez2

1Nutrition Laboratory, Faculty of Nutrition, University of Veracruz, Doctors and Dentists 910210, Forest Unit, Xalapa, Mexico. 2Pharmacochemistry Research Laboratory, Faculty of Biological-Chemical Sciences, University Autonomous of Campeche; Humberto Lanz Cárdenas s/n, Ex Hacienda Kalá, C.P. 24085, Campeche, Mexico.


Abstract

Prostate cancer is one of the leading causes of death among men worldwide; Some data suggest that ribosomal S6 p90 kinase (RSK 1-4), which belongs to the group of highly conserved Ser/Thr kinases, has been related to an increase in prostate cancer levels. For this reason, the aim of this study was to evaluate the theoretical interaction of some quinolone derivatives (compounds 1-19) with RSK-4 using 6rv2 protein and RSK-14 inhibitor (LJH685) in a docking model. The results showed that some quinolone derivatives (12, 15, 17, and 18) could interact with the 6rv2 protein surface in a different manner than LJH685. This phenomenon could be translated as greater RSK-14 inhibition, resulting in a decrease in prostate cancer levels. Analyzing these data, these quinolone derivatives could be considered good compounds to treat prostate cancer.

Keywords: Cancer, Quinolone, RSK-4, Docking


Introduction

Cancer is one of the main causes of death worldwide, which translates into a decrease in the life expectancy population.[1] There are several molecular mechanisms involved in the proliferation of cancer; for example, prostate cancer progression is related to androgen receptor activation.[2] It is important to mention that although there are some androgen receptor inhibitor drugs,[3,4] in some cases, resistance to drug therapy (castrate-resistant prostate cancer)[5] has led to the search for new treatments for this clinical pathology. In this way, a benzenesulfonamide derivative (Y08060) was developed as a bromodomain-containing protein 4 inhibitor for treating prostate cancer.[6] Furthermore, several triazole analogs were synthesized with antiandrogenic activity for prostate cancer.[7] Another study showed that some trioxane dimers interfere with the G0/G1 cell cycle using human prostate cancer cell lines.[8] In addition, a report showed that some carboxamide analogs could be used for castration-resistant prostate cancer through AKR1C3 inhibition (type 5 17β-hydroxysteroid dehydrogenase/prostaglandin F synthase.[9] Another study showed that quinolone derivative (FPA-137) might act as a proteasome inhibitor in human prostate cancer cells.[10]

On the other hand, some studies suggest that ribosomal S6 p90 kinase (RSK 1-4), which belongs to the group of highly conserved Ser/Thr kinases,[11] has been related to an increase in prostate cancer. For example, a study showed the Inhibition of RSK and YB-1 (Y-box; regulates androgen receptor expression)[12, 13] signaling enhances the anti-cancer effect of enzalutamide in prostate cancer.[14] In addition, a report showed that S6 PMD-026 drug acts as an inhibitor of RSK in combination with enzalutamide in castration-resistant prostate cancer patients.[15] Another theoretical study showed that a bis-phenol pyrazole derivative could be used as an inhibitor of the N-terminal kinase of RSK-2 in cancer cells.[16] In addition, other reports showed that RSK-2 is related to changes in the levels of prostate-specific antigen (a diagnostic marker for prostate cancer); however, in the presence of 3Ac-SL0101 (sk2 inhibitor), the expression of prostate-specific antigen is decreased.[17, 18]

All this data suggests that some drugs produce effects on prostate cancer; however, the data that exists in the literature on the interaction of some drugs with RSK in prostate cancer are few and very confusing. Perhaps this is due to the
 

 

 

 

 

diverse experimental designs that focus on multiple molecular mechanisms involved in this clinical pathology. Analyzing these data, the objective of this study was to evaluate the interaction of 19 quinolone derivatives on RSK-4 using a theoretical model.

Materials and Methods

Some quinolone derivatives (Figure 1) were used to evaluate the possible interaction with both the androgen receptor and RSK-4 as follows:

Figure 1. Chemical structure of Dibenzo derivatives

1= 1-ethyl-2(1H)-quinolone[19]

2= 1-methyl-6-nitro-2(1H)-quinolone[20]

3= 2-(2-quinolinyl)-1-[4-(trifluoromethyl)phenyl]ethanone[21]

4= 2-chloro-1-(8-hydroxy-5-quinolinyl)ethanone[22]

5= 2-cyano-3-phenyl-N-(quinoline-3-yl)acrylamide[23]

6= 4-chloro-6-(3,4-dihydro-1(2h)-quinolinyl)-2-pyrimidinamine[24]

7= 4-cyclohexyl-2(1h)-quinolone[25]

8= 4-Hydroxy-1-methyl-2(1H)-quinolone[26]

9= 5,7-dibromo-8-quinolinyl 4-nitrobenzoate[27]

10=6-methoxy-8-[(2-furanylmethyl)amino]-4-methyl-5-(3-trifluoromethylphenyloxy)quinolone[28]

11= 6-Quinolinyl trifluoromethanesulfonate[29]

12= 8-(Bromomethyl)quinoline[30]

13= 8-quinolinyl n-(3-bromophenyl)carbamate[31]

14=Cipriploxacine(1-cyclopropyl-6-fluoro-4-oxo-7-piperazine-1-ylquinoline-3-carboxylic acid)[32]

15 = 2-(Bromomethyl)quinolone[33]

16 = 2-(Trifluoromethyl)quinolone[34]

17= N4-(7-Chloro-4-quinolinyl)-N1,N1-dimethyl-1,4-pentanediamine[35]

18= 8-Hydroxyquinoline[36]

19=Flumequine (7-fluoro-12-methyl-4-oxo-1-azatricyclo[7.3.1.0][5,13]trideca-2,5,7,9(13)-tetraene-3-carboxylic acid)[37]

 

Ligand-protein complex

The interaction of quinone derivatives with RSK-4 was evaluated using 6rv2[38] protein and LJH685 (2,6-Difluoro-4-[4-[4-(4-methylpiperazin-1-yl)phenyl]pyridin-3-yl]phenol)[39] as theoretical tools. Besides, to evaluate the types of binding energy involved in the interaction of quinolone derivatives with the 6rv2[40] protein surface, the Docking Server software was used.[41]

Pharmacokinetics parameter

Pharmacokinetic parameters were determined using the Swiss ADME software.[42]

Toxicity analysis

Toxicity produced by quinolone derivatives (12, 15, 17, and 18) and RSK-14 inhibitor (LJH685) were evaluated using GUSAR software.[43]

Results and Discussion

There are several studies that indicate that quinolone derivatives could exert anti-cancerogenic activity;[44,45]  however, these data are not very clear. Therefore it is necessary to delve deeper into the possible anticancerigenic activity of these compounds. In this way, in this study, the interaction of 19 quinolone derivatives on RSK-4 was evaluated using 6rv2 protein and LJH685 (RSK-4 inhibitor)[39] as a theoretical tool in a Docking model.[41] The results (Table 1 and Figure 2) showed that LJH685 interacts with different amino acid residues (Phe84; Lys113; Arg197; Ser220; Lys221; Phe233; Cys234; Arg247; His250)involved in the 6rv2 protein surface compared with quinolone derivatives (1 to 19); this data suggest that this interaction is due to different functional groups involved in the chemical structure of each quinolone derivatives (Table 1 and Figure 2)

Table 1. Aminoacid residues involved in the interaction of LJH685 and quinolone derivatives (compounds 1-19) with 6rv2-protein surface.

Compound

Aminoacid residues

LJH685

Phe84; Lys113; Arg197; Ser220; Lys221; Phe233; Cys234; Arg247; His250

1

Arg7; Leu11; Val243; Phe246; Met247; Asn250

2

Arg7; Leu11; Val243; Phe246; Met247; Asn250

3

Arg7; Ala10; Leu11; Cys14; Phe246; Met249

4

Arg7; Leu11; Val243; Phe246; Met247; Asn250

5

Arg7; Leu11; Val242; Val243; Phe246; Met247; Asn250

6

Arg3; Arg7; Leu11; Phe246; Met249

7

Arg7; Leu11; Val243; Phe246; Met247; Met249; Asn250

8

Arg3; Val6; Arg7; Met249

9

Leu11; Val242; Val243; Phe246; Met247; Asn250

10

Arg7; Thr8; Leu11; Val242; Val243; Phe246; Met249; Asn250

11

Arg7; Leu11; Val242; Val243; Phe246; Met247; Asn250

12

Arg7; Thr8; Leu11; Phe246; Met247; Asn250

13

Arg7; Leu11; Val243; Phe246; Met249

14

Arg7; Leu11; Val243; Phe246; Met247; Met249; Asn250

15

Arg7; Leu11; Val242; Val243; Phe246

16

Arg7; Leu11; Phe246; Met247; Asn250

17

Leu11; Val242; Val243; Phe246; Met247

18

Leu11; Val243; Phe246; Met247

19

Arg3; Arg7; Ala10; Leu11; Cys14; Phe246; Met249

 

Figure 2. The scheme displayed the coupling site of amino acid residues involved in the interaction of quinolone derivatives with the 6rv2 protein surface. Visualized with GL mol viewer, docking server

On the other hand, it is important to mention that there are some reports which suggest that the interaction protein-ligand complex depends on energy levels which may determine their stability.[46] Besides, some thermodynamics reports showed the following;  i) free energy of binding can determine the energy value that requires a molecule to interact with a protein in a water environment; ii) electrostatic energy is the product of electrical charge and electrostatic potential, which are involved in the ligand-protein system; iii) total intermolecular energy may exert changes in the interaction protein-ligand, and iv) van der Waals (vdW) + hydrogen bond (H-bond) + desolvation energy (which have an influence on the movement of water molecules into or out of the ligand-protein system).[46] Analyzing these data, several thermodynamic parameters involved in the interaction of quinolone derivatives with the 6rv2 protein surface were evaluated in this investigation. The results (Table 2) displayed that the inhibition constant for compound 12 is lower than LJH685, compounds 1-11, and 13-19, which may result in greater interaction with the 6rv2 protein surface. In addition, the inhibition constant for compounds 15, 17, and 18 was lower compared to 1-11, 13, 14, and 19. This phenomenon could produce changes in the biological activity of RSK-4, translated as a possible decrease in prostate cancer levels.

Table 2. Thermodynamic parameters involved in the interaction of quinolone derivatives with 6rv2-protein surface.

Compound

A

B

C

D

E

F

LJH685

-7.60

2.67

-6.39

-1.28

-7.67

624.82

1

-4.12

951.24

-4.43

+0.01

-4.42

444.59

2

-4.75

330.89

-5.02

-0.02

-5.05

459.08

3

-5.32

125.58

-5.80

-0.03

-5.83

559.86

4

-4.61

420.50

-4.66

+0.00

-4.66

473.39

5

-5.06

196.85

-6.20

+0.00

-6.20

604.06

6

-5.69

67.14

-5.96

-0.03

-5.99

553.31

7

-5.31

127.42

-5.63

+0.02

-5.61

519.25

8

-4.39

609.13

-3.31

-1.08

-4.39

398.90

9

-6.08

35.14

-6.53

+0.00

-6.52

530.45

10

-6.32

23.21

-6.74

+0.01

-6.73

660.84

11

-4.31

697.92

-5.31

-0.03

-5.34

478.36

12

-3.94

1.30

-4.23

-0.00

-4.23

410.80

13

-5.44

103.59

-5.93

-0.01

-5.94

570.68

14

-5.09

186.23

-5.97

-0.09

-6.06

607.72

15

-3.70

1.93

-4.00

+0.00

-4.00

406.73

16

-4.45

544.70

-4.69

-0.06

-4.75

410.04

17

-2.85

8.10

-4.87

+0.25

-4.62

563.56

18

-3.13

5.09

-3.40

-0.03

-3.43

371.03

19

-5.40

110.30

-4.69

-1.01

-5.70

499.25

A = Est: Free Energy of Binding (kcal/mol)

B = Est. Inhibition Constant, Ki (mM)

C = vdW + Hbond + desolv Energy (kcal/mol)

D = ElectrostaticEnergy (kcal/mol)

E = Total Intermolec. Energy (kcal/mol)

F = Interact. Surface

Pharmacokinetic evaluation

There are several reports to predict some pharmacokinetic parameters using different methods.[47-49] In this research, some pharmacokinetic parameters involved in the chemical structure of quinolone derivatives were evaluated using Swiss ADME software (Table 3).

Table 3. Pharmacokinetic parameters involved in the chemical structure of quinolone derivatives

Parameter

LJH685

12

15

17

18

GI absorption

High

High

High

High

High

BBB permeant

Yes

Yes

Yes

Yes

Yes

P-GP substrate

Yes

No

No

No

No

CYP1A2 inhibitor

Yes

Yes

Yes

Yes

Yes

CYP2C19 inhibitor

Yes

Yes

Yes

No

No

CYP2C9 inhibitor

No

No

No

No

No

CYP2D6  inhibitor

Yes

No

No

Yes

No

CYP3A4 inhibitor

Yes

No

No

Yes

No

Consensus LogPO/W

3.76

2.98

2.98

4.15

1.76

 

The results displayed differences in gastrointestinal absorption and metabolism (involving different types of cytochrome P450 systems). This phenomenon could depend on the chemical structure of each quinolone derivative.

Toxicity analysis

Some data in the literature indicate that quinolone can produce toxicity in different biological models.[50] Analyzing this data, the possible toxicity produced by some quinolone derivatives (12, 15, 17, and 18) was evaluated using the GUSAR software.[43] The results showed that compounds 12, 15, and 18 require a higher dose to produce toxicity (LD50) via oral compared with RSK-14 inhibitor (LJH685). This data suggest that toxicity could be dose-dependent and the routes of administration for each quinolone derivative.

Table 4. Possible toxicity involved in the administration of quinolone derivatives (12, 15, 17, and 18) and LJH685 using Gusar Software.

Compound

IP LD50 (mg/kg)

IV LD50 (mg/kg)

Oral LD50 (mg/kg)

SC LD50 (mg/kg)

LJH685

339.70

78.62

291.30

353.70

12

218.00

60.73

502.90

315.10

15

174.80

57.35

650.70

511.10

17

102.50

48.29

33.60

342.40

18

245.30

63.77

1028.00

593.00

Conclusion

Theoretical evaluation of the interaction of quinolone derivatives with the 6rv2 protein surface suggests that quinoline derivatives 12, 15, 17, and 18 may have a higher affinity for the 6rv2 protein. This phenomenon could be translated as greater RSK-14 inhibition, resulting in a decrease in prostate cancer levels. Analyzing these data, these quinolone derivatives could be considered good compounds to treat prostate cancer.

Acknowledgments

None.

Conflict of interest

None.

Financial support

None.

Ethics statement

None.

References

1.        Pienta K, Gorin M, Rowe S, Carroll P, Pouliot F, Probst S. A phase 2/3 prospective multicenter study of the diagnostic accuracy of prostate-specific membrane antigen PET/CT with 18F-DCFPyL in prostate cancer patients (OSPREY). J Urol. 2021;206(1):52-61.

2.        Mitsiades N, Kaochar S. Androgen receptor signaling inhibitors: post-chemotherapy, pre-chemotherapy and now in castration-sensitive prostate cancer. Endo Rel Cancer. 2021;28(8):T19-38.

3.        Delaere K, Thillo E. Flutamide monotherapy as primary treatment in advanced prostatic cancer. Sem Oncol. 1991;18(suppl 1):13-8.

4.        Gomez J, Dupont A, Cusan L, Tremblay M, Tremblay M, Labrie F. Simultaneous liver and lung toxicity related to the nonsteroidal antiandrogen nilutamide (Anandron): a case report. Am J Med. 1992;92(5):563-6.

5.        Watson P, Arora V, Sawyers C. Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer. Nature Rev Cancer. 2015;15(12):701-11.

6.        Xiang Q, Zhang Y, Li J, Xue X, Wang C, Song M, et al. Y08060: a selective BET inhibitor for treatment of prostate cancer. Med Chem Lett. 2018;9(3):262-7.

7.        Ferroni C, Pepe A, Kim Y, Lee S, Guerrini A, Parenti M, et al. 1, 4-Substituted triazoles as nonsteroidal antiandrogens for prostate cancer treatment. Med Chem Lett. 2017;60(7):3082-93.

8.        Alagbala A, McRiner A, Borstnik K, Labonte T, Chang W, D'Angelo J, et al. Biological mechanisms of action of novel C-10 non-acetal trioxane dimers in prostate cancer cell lines. J Med Chem. 2006;49(26):7836-42.

9.        Endo S, Oguri H, Segawa J, Kawai M, Hu D, Xia S, et al. Development of novel AKR1C3 inhibitors as new potential treatment for castration-resistant prostate cancer. J Med Chem. 2020;63(18):10396-411.

10.      Adsule S, Barve V, Chen D, Ahmed F, Dou Q, Padhye S, et al. Novel Schiff base copper complexes of quinoline-2 carboxaldehyde as proteasome inhibitors in human prostate cancer cells. J Med Chem. 2006;49(24):7242-6.

11.      Xu J, Jia Q, Zhang Y, Yuan Y, Xu T, Yu K, et al. Prominent roles of ribosomal S6 kinase 4 (RSK4) in cancer. Path Res Pract. 2021;219:153374.

12.      Shiota M, Takeuchi A, Song Y, Yokomizo A, Kashiwagi E, Uchiumi T et al. Y-box binding protein-1 promotes castration-resistant prostate cancer growth via androgen receptor expression. Endoc Rel Cancer. 2011;18(4):505.

13.      Shiota M, Sekino Y, Tsukahara S, Abe T, Kinoshita, F, Imada, K. Gene amplification of YB‐1 in castration‐resistant prostate cancer in association with aberrant androgen receptor expression. Cancer Sci. 2021;112(1):323-30.

14.      Shiota M, Fujimoto N, Imada K, Yokomizo A, Itsumi, M, Takeuchi A. Potential role for YB-1 in castration-resistant prostate cancer and resistance to enzalutamide through the androgen receptor V7. JNCI: J Nat Cancer Inst. 2016;108(7):1-10.

15.      Ushijima M, Shiota M, Matsumoto T, Kashiwagi E, Inokuchi J, Eto M. An oral first‐in‐class small molecule RSK inhibitor suppresses AR variants and tumor growth in prostate cancer. Cancer Sci. 2022;113(5):1731-8.

16.      Jain R, Mathur M, Lan J, Costales A, Atallah G, Ramurthy S. Discovery of potent and selective RSK inhibitors as biological probes. J Med Chem. 2015;8(17):6766-83.

17.      Smith J, Maloney D, Clark D, Xu Y, Hecht S, Lannigan D. Influence of rhamnose substituents on the potency of SL0101, an inhibitor of the Ser/Thr kinase, RSK. Bioorg Med Chem, 2006;14(17):6034-42.

18.      Hilinski M, Mrozowski R, Clark D, Lannigan D. Analogs of the RSK inhibitor SL0101: optimization of in vitro biological stability. Bioorg Med Chem Lett. 2012;22(9):3244-7.

19.      Ukrainets I, Sidorenko L, Gorokhova O, Bereznyakova N, Shishkina S. 4-hydroxy-2-quinolones. 109. Alkylation of 4-substituted ethyl 2-oxo-1, 2-dihydro-quinoline-3-carboxylates. ChemHeter Comp. 2006;42(10):1296-300.

20.      Demidov O, Pobedinskaya D, Borovleva A, Avakyan E, Ermolenko A, Aksenov A. SNH-Arylamination of 1-methylquinolin-2 (1H)-one Nitro Derivatives. Chem Heter Comp. 2021;57(2):166-74.

21.      Schymanski E, Chirsir P, Kondic T, Thiessen P, Zhang X, Bolton E. PFAS and Fluorinated Compounds in PubChem Tree. 2022:1-14. Available from: https://gitlab.lcsb.uni.lu/eci/pubchem-docs/-/raw/main/pfas-tree/ PFAS_Tree.pdf?inline=false

22.      Leonardi M, Estévez V, Villacampa M, Menéndez J. The Hantzsch pyrrole synthesis: non-conventional variations and applications of a neglected classical reaction. Synthesis. 2019;51(4):816-28.

23.      Idris M, Adeniji S, Habib K, Adeiza. A Molecular docking of some novel quinoline derivatives as potent inhibitors of human breast cancer cell line. Lab-in-Silico. 2021;2(1):30-7.

24.      PATENTSCOPE (WIPO). SID 389194554. Available from: https://pubchem.ncbi.nlm.nih.gov/substance/389194554

25.      Katzarov S, Behrends V. Temporal Hierarchy and Context-Dependence of Quorum Sensing Signal in Pseudomonas aeruginosa. Life. 2022;12(12):1-12.

26.      Amani A, Khazalpour S, Nematollahi D. Electrochemical oxidation of acetaminophen and 4-(piperazin-1-yl) phenols in the presence of 4-hydroxy-1-methyl-2 (1H)-quinolone. J Electroch Soc. 2012;160(1):H33.

27.      PATENTSCOPE (WIPO).SID 391042909. Available from: https://pubchem.ncbi. nlm.nih.gov/substance/391042909

28.      Shi A, Nguyen T, Battina S, Rana S, Takemoto D, Chiang P. Synthesis and anti-breast cancer activities of substituted quinolines. Bioorg Med Chem Lett. 2008;18(11):3364-8.

29.      Kassanova A, Krasnokutskaya E, Beisembai P, Filimonov V.  A Novel Convenient Synthesis of Pyridinyl and Quinolinyl Triflates and Tosylates via One-Pot Diazotization of Aminopyridines and Aminoquinolines in Solution. Synthesis. 2016;48(02):256-62.

30.      Tulyaganov T, Allaberdiev F. Alkaloids from plants of the Nitraria genus. Structure of sibiridine. Chem Nat Comp. 2003;39(3):292-3.

31.      Licence, MLS003171375. Available from: https://dtp.cancer.gov/dtpstandard/ servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=377851

32.      Campoli-Richards DM, Monk JP, Price A, Benfield P, Todd PA, Ward A. Ciprofloxacin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs. 1988;35(4):373-447. 

33.      Holmes A, Simpson S, Canary J. Stereodynamic coordination complexes. Dependence of exciton coupled circular dichroism spectra on molecular conformation and shape. Monat Für Chem. 2005;136(3):461-75.

34.      López S, Rebollo O, Salazar J, Charris J, Yánez C. Synthesis of 2-trifluoromethyl-1 (substituted aryl)-4 (1H)-quinolones using trifluoroacetamidoyl chlorides. J Fluorine Chem. 2003;120(1):71-5.

35.      Furuseth S, Karlsen J, Mostad A, Rømming C, Salmen R, Tønnesen H. N4-(7-Chloro-4-quinolinyl)-N1, N1-diethyl-1, 4-pentanediamine. An X-ray diffraction study of chloroquine diphosphate hydrate. ActaChem Scan. 1989;44(7):741-5.

36.      Singh D, Nishal V, Bhagwan S, Saini R, Singh I. Electroluminescent materials: Metal complexes of 8-hydroxyquinoline-A review. Mat Des. 2018;156:215-28.

37.      Palominos R, Freer J, Mondaca M, Mansilla H. Evidence for hole participation during the photocatalytic oxidation of the antibiotic flumequine. J Photochem Photobiol. 2008;193(2-3):139-45.

38.      Zúñiga R, Mancilla D, Rojas T, Vergara F, González W, Catalán M. A Direct Interaction between Cyclodextrins and TASK Channels Decreases the Leak Current in Cerebellar Granule Neurons. Biology. 2022;11(8):1097.

39.      Zhang S, Liu J, Lu ZY, Xue YT, Mu XR, Liu Y, et al. Combination of RSK inhibitor LJH-685 and FLT3 inhibitor FF-10101 promoted apoptosis and proliferation inhibition of AML cell lines. Cell Oncol (Dordr). 2022;45(5):1005-18.

40.      Ramírez D, Mejia-Gutierrez M, Insuasty B, Rinne S, Kiper A, Platzk M. 5-(Indol-2-yl) pyrazolo [3, 4-b] pyridines as a new family of task-3 channel blockers: A pharmacophore-based regioselective synthesis. Molecules. 2021;26(13):3897.

41.      Figueroa-Valverde L, Rosas-Nexticapa M, Montserrat M, Díaz-Cedillo F, López-Ramos M, Alvarez-Ramirez M. Synthesis and Theoretical Interaction of 3-(2-oxabicyclo [7.4. 0] trideca-1 (13), 9, 11-trien-7-yn-12-yloxy)-steroid Deriva-tive with 17β-hydroxysteroid Dehydrogenase Enzyme Surface. Biointerface Res Appl Chem. 2023;13:266.

42.      Lauro F, Marcela R, Mari L, Magdalena A, Virginia M, Francisco D. Evaluation of Biological Activity of a Diazocine Derivative against Heart Failure Using an Ischemia-Reperfusion Injury Model. Drug Res. 2022;72(07):404-11.

43.      Vishal K, Singla C, Sharma A, Dhiman A. Prediction of Environmental Toxicity of Active Chemical Constituents of Ipomoea Carnea through GUSAR Software. Turkish J Comp Math Educ. 2020;11(2):735-40.

44.      Gao F, Zhang X, Wang T, Xiao J. Quinolone hybrids and their anti-cancer activities: An overview. Eur J Med Chem. 2019;165:59-79.

45.      Paul M, Gafter A, Fraser A, Leibovici L. The anti-cancer effects of quinolone antibiotics?. Eur J Clin Microbiol Infect Dis. 2007;26(11):825-31.

46.      Verkhivker G, Bouzida D, Gehlhaar D, Rejto P, Arthurs S, Colson A. Deciphering common failures in molecular docking of ligand-protein complexes. J Comp Mol Des. 2000;14(8):731-51.

47.      Levitt D. PKQuest: a general physiologically based pharmacokinetic model. Introduction and application to propranolol. BMC Clin Pharmacol. 2012;2(1):1-21.

48.      Bourne D. Using the Internet as a pharmacokinetic resource. Clin Ppharmacokinet. 1997;33(3):153-60.

49.      Sicak Y. Design and antiproliferative and antioxidant activities of furan-based thiosemicarbazides and 1, 2, 4-triazoles: their structure-activity relationship and Swiss ADME predictions. Med Chem Res. 2021;30(8):1557-68.

50.      Stahlmann R, Lode, H. Toxicity of quinolones. Drugs. 1999;58(2):37-42.

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