Design, Synthesis, and Antimicrobial Activity Evaluation of Ciprofloxacin—Indole Hybrids
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Pharmacology
2.2.1. Antibacterial Activity
2.2.2. Propensity for the Development of Bacterial Resistance
2.2.3. Evaluation of Bacterial Resistance Development
2.3. Cytotoxic Activity
2.4. Molecular Docking and Drug-like Properties Prediction
3. Materials and Methods
3.1. Chemical Part
3.1.1. Synthesis Procedure of 1-(3-Bromopropyl)-1H-indole-3-carbaldehyde (1)
3.1.2. Synthesis Procedure of Ciprofloxacin–Indole Hybrid 2
3.1.3. Synthesis Procedure of Ciprofloxacin–Indole Hybrid 3a
3.1.4. Synthesis Procedure of Ciprofloxacin–Indole Hybrid 3b
3.1.5. Synthesis Procedure of Ciprofloxacin–Indole Hybrid 3c
3.1.6. Synthesis Procedure of Ciprofloxacin–Indole Hybrid 3d
3.1.7. Synthesis Procedure of 1-(4-Bromobutyl)-1H-indole-3-carbaldehyde (4a)
3.1.8. Synthesis Procedure of 1-(5-Bromopentyl)-1H-indole-3-carbaldehyde (4b)
3.1.9. Synthesis Procedure of Ciprofloxacin–Indole Hybrid 5a
3.1.10. Synthesis Procedure of Ciprofloxacin–Indole Hybrid 5b
3.1.11. Synthesis Procedure of Ciprofloxacin–Indole Hybrid 6a
3.1.12. Synthesis Procedure of Ciprofloxacin–Indole Hybrid 6b
3.1.13. Synthesis Procedure of Ciprofloxacin–Acetophenone Hybrid 7a
3.1.14. Synthesis Procedure of Ciprofloxacin–Acetophenone Hybrid 7b
3.1.15. Synthesis Procedure of Ciprofloxacin–Acetophenone Hybrid 8a
3.1.16. Synthesis Procedure of Ciprofloxacin–Acetophenone Hybrid 8b
3.2. Pharmacological Assays
3.2.1. Antibacterial Activity Evaluation
3.2.2. Propensity Evaluation for the Development of Bacterial Resistance
3.2.3. Time-Kill Assay
3.3. Evaluation of Cytotoxicity Activity In Vitro
3.4. Molecular Docking and Drug-like Properties Prediction
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
References
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Compound | Gram-Positive Strains | Gram-Negative Strains | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
26003 a | 6538 b | 25923 c | 336931 d | 29212 e | 63501 f | 25922 g | 44568 h | 44103 i | 27853 j | 10104 k | |
2 | 4 | 0.5 | 0.5 | 4 | 0.5 | 0.5 | 8 | 0.5 | 0.5 | 8 | 0.5 |
3a | 4 | 0.25 | 0.25 | 4 | 0.5 | 1 | 8 | 0.25 | 0.25 | 4 | 0.5 |
3b | 4 | 4 | 4 | 16 | 32 | 2 | 16 | 8 | 4 | 8 | 8 |
3c | 4 | 4 | 2 | 4 | 32 | 2 | 16 | 2 | 2 | 8 | 4 |
3d | 4 | 2 | 1 | 4 | 8 | 1 | 16 | 1 | 1 | 8 | 2 |
5a | 2 | 1 | 0.5 | 8 | 1 | 1 | 4 | 1 | 1 | 4 | 2 |
5b | 16 | 4 | 1 | 16 | 4 | 16 | 32 | 2 | 2 | 16 | 8 |
6a | 8 | 0.5 | 0.5 | 8 | 1 | 4 | 16 | 0.5 | 0.5 | 8 | 2 |
6b | 8 | 2 | 0.5 | 16 | 8 | 8 | 16 | 1 | 4 | 16 | 16 |
7a | 2 | 1 | 0.5 | 2 | 1 | 1 | 2 | 2 | 2 | 8 | 4 |
7b | 0.5 | 0.5 | 0.125 | 1 | 0.5 | 0.5 | 1 | 0.5 | 0.5 | 2 | 1 |
8a | 0.5 | 0.5 | 0.25 | 2 | 0.25 | 1 | 1 | 0.25 | 0.5 | 8 | 2 |
8b | 0.25 | 0.25 | 0.0625 | 0.5 | 0.25 | 0.25 | 0.5 | 0.25 | 0.125 | 1 | 0.5 |
Ciprofloxacin | 0.25 | 0.25 | 0.25 | 0.25 | 0.25 | 0.25 | 0.25 | 0.25 | 0.125 | 1 | 0.5 |
Norfloxacin | 0.5 | 0.5 | 0.5 | 16 | 1 | 2 | 2 | 0.5 | 0.5 | 2 | 4 |
Penicillin | 0.5 | 2 | 0.5 | 2 | >32 | >32 | >32 | >32 | >32 | >32 | 32 |
Compounds | MDR Gram-Positive Strains | MDR Gram-Negative Strains | |
---|---|---|---|
43300 a | 33591 b | BAA-196 c | |
2 | 2 | 2 | 16 |
3a | 0.5 | 0.5 | 4 |
3b | 16 | 8 | 32 |
3c | 16 | 4 | 32 |
3d | 8 | 4 | 16 |
5a | 1 | 2 | 8 |
5b | 4 | 4 | 32 |
6a | 8 | 4 | 32 |
6b | 4 | 16 | 16 |
7a | 1 | 1 | 1 |
7b | 0.5 | 0.5 | 1 |
8a | 0.5 | 1 | 0.5 |
8b | 0.25 | 0.25 | 0.25 |
Ciprofloxacin | 0.25 | 0.25 | 0.25 |
Norfloxacin | 0.5 | 0.5 | 0.5 |
Penicillin | 32 | >32 | >32 |
Compoud | MW | CLogP | HBD | HBA | n-ROTB | Lipinski’s Violation |
---|---|---|---|---|---|---|
Rule | ≤500 | ≤5 | ≤5 | <10 | ≤10 | ≤1 |
2 | 516.57 | 1.80 | 1 | 8 | 8 | 1 |
3a | 573.63 | 1.41 | 4 | 11 | 9 | 2 |
3b | 589.70 | 1.95 | 4 | 10 | 10 | 1 |
3c | 634.71 | 3.17 | 2 | 10 | 10 | 1 |
3d | 545.62 | 1.80 | 1 | 9 | 9 | 1 |
5a | 530.60 | 2.07 | 1 | 8 | 9 | 1 |
5b | 544.63 | 2.67 | 1 | 8 | 10 | 1 |
6a | 587.66 | 1.68 | 4 | 11 | 10 | 2 |
6b | 601.18 | 2.19 | 4 | 11 | 11 | 3 |
7a | 479.51 | 1.10 | 1 | 8 | 7 | 0 |
7b | 483.93 | 1.72 | 1 | 7 | 6 | 0 |
8a | 536.56 | 0.52 | 4 | 11 | 8 | 2 |
8b | 540.98 | 1.14 | 4 | 10 | 7 | 1 |
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Song, M.; Hua, Y.; Liu, Y.; Xiao, X.; Yu, H.; Deng, X. Design, Synthesis, and Antimicrobial Activity Evaluation of Ciprofloxacin—Indole Hybrids. Molecules 2023, 28, 6325. https://doi.org/10.3390/molecules28176325
Song M, Hua Y, Liu Y, Xiao X, Yu H, Deng X. Design, Synthesis, and Antimicrobial Activity Evaluation of Ciprofloxacin—Indole Hybrids. Molecules. 2023; 28(17):6325. https://doi.org/10.3390/molecules28176325
Chicago/Turabian StyleSong, Mingxia, Yi Hua, Yuxin Liu, Xunli Xiao, Haihong Yu, and Xianqing Deng. 2023. "Design, Synthesis, and Antimicrobial Activity Evaluation of Ciprofloxacin—Indole Hybrids" Molecules 28, no. 17: 6325. https://doi.org/10.3390/molecules28176325