Synthesis, Characterization and Biological Evaluation of Some Quinoxaline Derivatives: A Promising and Potent New Class of Antitumor and Antimicrobial Agents
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Pharmacological Screening
2.2.1. In Vitro Anticancer Screening
Compound No. | IC50 (μg/mL) | |||
---|---|---|---|---|
MCF-7 | NCI-H460 | SF-268 | WI 38 | |
3 | 36.02 ± 7.33 c | 26.74 ± 2.18 b | 30.64 ± 2.39 b | 32.16 ± 6.54 |
4 | 0.02 ± 0.006 a | 0.01 ± 0.004 a | 0.06 ± 0.003 a | non-cytotoxic |
5a | 0.01 ± 0.001 a | 0.02 ± 0.006 a | 0.02 ± 0.008 a | non-cytotoxic |
5b | 0.02 ± 0.002 a | 0.01 ± 0.002 a | 0.06 ± 0.008 a | non-cytotoxic |
6 | 22.41 ± 10.4 b | 30.48 ± 10.8 b | 26.51 ± 2.87 b | 28.25 ± 0.87 |
7 | 26.4 ± 2.10 b | 12.42 ± 3.01 b | 10.63 ± 2.83 b | non-cytotoxic |
8 | 42.16 ± 2.46 c | 26.60 ± 2.63 b | 35.32 ± 12.81 c | 10.59 ± 5.51 |
9 | 37.07 ± 7.34 c | 16.37 ± 2.32 b | 38.94 ± 2.63 c | 30.62 ± 6.21 |
11 | 1.18 ± 1.03 a | 2.83 ± 0.53 a | 2.86 ± 4.92 a | 56.85 ± 4.05 |
12 | 35.22 ± 4.18 c | 34.03 ± 6.05 c | 22.10 ± 2.81 b | 22.97 ± 8.2 |
13 | 37.64 ± 6.72 c | 36.05 ± 5.23 c | 29.35 ± 7.01 c | 18.62 ± 1.21 |
14 | 30.32 ± 3.86 b | 38.32 ± 2.35 c | 42.06 ± 5.58 c | 58.70 ± 8.65 |
15 | 28.42 ± 5.80 b | 22.73 ± 8.12 b | 30.24 ± 2.04 b | 18.16 ± 4.03 |
16 | 12.82 ± 1.46 b | 22.95 ± 0.46 b | 49.85 ± 8.64 c | 30.03 ± 2.36 |
17 | 21.23 ± 0.14 b | 15.81 ± 0.10 b | 21.33 ± 2.12 b | 21.40 ± 2.02 |
DMSO | 0 | 0 | 0 | 0 |
Doxorubicin | 0.04 ± 0.008 | 0.09 ± 0.008 | 0.09 ± 0.007 | non-cytotoxic |
2.2.2. Antimicrobial Activity
Antibacterial Activity
Antifungal Activity
Compound No. | Inhibition Zone Diameter (IZ) (mm) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Gram Positive Bacteria | Gram Negative Bacteria | Fungi | ||||||||
Bacillus subtilis | Staphylococcus aureus | Streptococcus faecalis | Escherichia coli | Neisseria gonorrhoeae | Pseudomonas aeruginosa | Salmonella typhimurium | Aspergillus flavus | Aspergillus fumigatus | Candida albicans | |
3 | 15 | 14 | 14 | 13 | 14 | 14 | 13 | R | R | R |
4 | 20 | 26 | 18 | 17 | 21 | 21 | 17 | 13 | 10 | 20 |
5a | 13 | 11 | 9 | 13 | R | 11 | 14 | R | 12 | 12 |
5b | 17 | 17 | 11 | 11 | R | 10 | 13 | R | 12 | 9 |
6 | 11 | 9 | 11 | 11 | 11 | 9 | 8 | R | R | R |
7 | 11 | 10 | 11 | 10 | 10 | 10 | 9 | R | R | R |
8 | 9 | 9 | 10 | 11 | 9 | 9 | 7 | R | R | R |
9 | 28 | 27 | 27 | 29 | 28 | 31 | 17 | R | 5 | 11 |
11 | 19 | 17 | 15 | 15 | R | 14 | 18 | R | R | R |
12 | 18 | 19 | 18 | 17 | R | 20 | 18 | R | R | R |
13 | 17 | 16 | 20 | 17 | R | 19 | 17 | R | R | R |
14 | 12 | 12 | 12 | 12 | 12 | 12 | 10 | R | R | R |
15 | 10 | 9 | 9 | 10 | 9 | 9 | 10 | R | R | R |
16 | 10 | 12 | 11 | 10 | 11 | 11 | 10 | R | R | R |
17 | 7 | 8 | 10 | 11 | 6 | 8 | 5 | R | R | R |
DMSO | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Ampicillin | 20 | 22 | 19 | - | - | - | - | - | - | - |
Gentamicin | - | - | - | 20 | 18 | 17 | 23 | - | - | - |
Amphotericin B | - | - | - | - | - | - | - | 17 | 23 | 19 |
Compound No. | Minimum Inhibitory Concentration (MIC) (µg/mL) | |||||||
---|---|---|---|---|---|---|---|---|
Gram positive Bacteria | Gram Negative Bacteria | Fungi | ||||||
Bacillus subtilis | Staphylococcus aureus | Streptococcus faecalis | Escherichia coli | Pseudomonas aeruginosa | Salmonella typhimurium | Aspergillus fumigatus | Candida albicans | |
3 | 1.95 | 3.9 | 15.63 | 3.9 | 125 | 1.95 | - | - |
4 | 0.98 | 3.9 | 0.98 | 3.9 | >125 | 0.98 | - | 3.9 |
5a | 31.25 | 62.5 | 62.5 | 125 | 125 | 31.25 | 31.25 | 62.5 |
5b | 1.95 | 1.95 | 3.9 | 1.95 | >125 | 1.95 | 1.95 | 3.9 |
9 | 0.98 | 1.95 | 0.98 | 1.95 | 125 | 0.98 | 0.98 | 0.98 |
10 | 0.98 | 0.98 | 0.98 | 3.9 | 125 | 1.95 | - | - |
11 | 0.98 | 7.81 | 62.5 | 62.5 | 125 | 7.81 | - | - |
13 | 1.95 | 7.81 | 62.5 | 7.81 | 125 | 3.9 | - | - |
14 | 1.95 | 1.95 | 1.95 | 3.9 | 125 | 1.95 | - | - |
16 | 1.95 | 1.95 | 31.25 | 3.9 | 125 | 1.95 | - | - |
3. Experimental Section
3.1. General Information
3.1.1. 6-Bromo-2-chloro-3-hydrazinylquinoxaline (3)
3.1.2. 8-Bromo-4-chlorotetrazolo[1,5-a]quinoxaline (4)
3.1.3. General Procedure for Synthesis of 8-Bromo-4-(substituted amino)tetrazolo[1,5-a]quinoxaline (5a,b)
8-Bromo-4-(piperidin-1-yl)tetrazolo[1,5-a]quinoxaline (5a)
8-Bromo-4-(morpholin-4-yl)tetrazolo[1,5-a]quinoxaline (5b)
3.1.4. 6-Bromo-2-chloro-3-(3,5-dimethyl-1H-pyrazol-1-yl)quinoxaline (6)
3.1.5. 7-Bromo-4-hydrazinyltetrazolo[1,5-a]quinoxaline (7)
3.1.6. 6-Bromo-2-chloro-3-[2-(4-chlorobenzylidene)hydrazinyl]quinoxaline (8)
3.1.7. 6-Bromo-2,3-dihydrazinylquinoxaline (9)
3.1.8. 9-Bromoditetrazolo[1,5-a:5′,1′-c]quinoxaline (11)
3.1.9. 7-Bromo-4,11-dimethyl-2,13-dihydrobis[1,2,4]triazino[4,3-a:3',4'-c]quinoxaline (12)
3.1.10. 9-Bromo-di-1,2,4-triazolo[1,5-a:5′,1′-c]quinoxaline (13)
3.1.11. 6-Bromo-3-(3,5-dimethyl-1H-pyrazol-1-yl)-2-hydrazinyl quinoxaline (14)
3.1.12. 6-Bromo-2,3-bis(3,5-dimethyl-1H-pyrazol-1-yl)quinoxaline (15)
3.1.13. 6-Bromo-2,3-bis(3-amino-1H-pyrazol-5(4H)-one)quinoxaline (16)
3.1.14. 6-Bromo-2,3-bis(3-methyl-1H-pyrazol-5(4H)-one)quinoxaline (17)
3.2. Pharmacological Evaluation
3.2.1. Anticancer Activity
Cell Cultures
Cancer Cell Growth Assay
3.2.2. Antimicrobial Activity
Preparation of Microbial Suspensions
Determination of Antimicrobial Activity by Disk Diffusion Method
Determination of Minimum Inhibitory Concentration (MIC)
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Al-Marhabi, A.R.; Abbas, H.-A.S.; Ammar, Y.A. Synthesis, Characterization and Biological Evaluation of Some Quinoxaline Derivatives: A Promising and Potent New Class of Antitumor and Antimicrobial Agents. Molecules 2015, 20, 19805-19822. https://doi.org/10.3390/molecules201119655
Al-Marhabi AR, Abbas H-AS, Ammar YA. Synthesis, Characterization and Biological Evaluation of Some Quinoxaline Derivatives: A Promising and Potent New Class of Antitumor and Antimicrobial Agents. Molecules. 2015; 20(11):19805-19822. https://doi.org/10.3390/molecules201119655
Chicago/Turabian StyleAl-Marhabi, Aisha R., Hebat-Allah S. Abbas, and Yousry A. Ammar. 2015. "Synthesis, Characterization and Biological Evaluation of Some Quinoxaline Derivatives: A Promising and Potent New Class of Antitumor and Antimicrobial Agents" Molecules 20, no. 11: 19805-19822. https://doi.org/10.3390/molecules201119655