Novel Guanidine Compound against Multidrug-Resistant Cystic Fibrosis-Associated Bacterial Species
Abstract
:1. Introduction
2. Materials and Methods
2.1. Reagents and Equipment
2.2. Synthesis of Compounds
2.3. Bacterial Strains
2.4. Antimicrobial Activity Assays
2.5. Checkerboard Assay
2.6. Cytotoxicity Assays
3. Results and Discussion
3.1. Chemistry
3.2. Biological Activity
3.2.1. Antimicrobial Evaluation of Newly Synthesized Compounds
3.2.2. Cytotoxic Evaluation of H-BDF
3.2.3. Synergistic Effects between H-BDF and Conventional Antibiotics
3.2.4. Activity of Compound H-BDF against Multidrug-Resistant Clinical Isolates Recovered from Respiratory Samples of CF Patients
4. Conclusions
5. Patents
Author Contributions
Acknowledgments
Conflicts of Interest
References
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Entry | R1 | R2 | R3 | Molecular Weight (g/mol) | Chemical Structure | P. aeruginosa PAO1 | B. cenocepacia J2315 | ||
---|---|---|---|---|---|---|---|---|---|
MIC (µg/mL) | MBC (µg/mL) | MIC (µg/mL) | MBC (µg/mL) | ||||||
1 | C10H15 a | C6H11 | 320.19 | | >128 | nd | >128 | nd | |
2 | C10H15 a | C6H5 | - | 314.45 | | >128 | nd | >128 | nd |
3 | C10H15 a | 3-F-4-CH3-C6H3 | - | 385.97 | | >128 | nd | >128 | nd |
4 | C10H15 a | 2-NO2-C6H4 | - | 359.44 | | >128 | nd | >128 | nd |
5 | C10H15 a | 4-CH3CO-C6H4 | - | 356.47 | | >128 | nd | >128 | nd |
6 | C10H15 a | 2,3-di-Cl-C6H3 | - | 383.34 | | >128 | nd | >128 | nd |
7 | C10H15 a | 2-Br-4,6-di-F-C6H2 | - | 428.32 | | >128 | nd | >128 | nd |
8 | C10H7 b | 2-Br-4,6-di-F-C6H2 | - | 421.97 | | >128 | nd | >128 | nd |
9 | 2,4-di-Cl-C6H3 | 2-Br-4,6-di-F-C6H2 | - | 439.88 | | >128 | nd | >128 | nd |
10 | 4-CH3-C6H4 | 2-Br-4,6-di-F-C6H2 | - | 385.97 | | >128 | nd | >128 | nd |
11 | C10H15 a | 2-Br-4,6-di-F-C6H2 | 2-Br-4,6-di-F-C6H2 | 603.2 | | 0.5 | 4 | 2 | 8 |
Tobramycin | 467.51 | 2 | 2 | >128 | >128 | ||||
Meropenem | 383.46 | 1 | 4 | 8 | 64 | ||||
Ceftazimide | 546.57 | 2 | 2 | 16 | 128 |
Compound | 11 (H-BDF) | 12 | 13 | Tobramycin | Meropenem | Ceftazimide |
---|---|---|---|---|---|---|
Organism | MIC/MBC | MIC/MBC | MIC/MBC | MIC/MBC | MIC/MBC | MIC/MBC |
Gram-negative bacteria | ||||||
Bordetella bronchiseptica 9.73H+ | 0.5/2 | 16/64 | >128/>128 | 64/64 | 0.125/0.25 | 8/64 |
Escherichia coli ATCC25922 | 1/2 | 64/64 | >128/>128 | 16/16 | 0.03125/0.0625 | 1/1 |
Pseudomonas aeruginosa PAO1 | 0.5/4 | 32/>128 | >128/>128 | 2/2 | 1/4 | 2/2 |
Burkholderia cenocepacia J2315 | 2/8 | 64/128 | >128/>128 | >128/>128 | 8/64 | 16/128 |
Pandorea apista DSM16535 | 1/2 | 64/128 | >128/>128 | 32/128 | >128/nd | 128/nd |
Gram-positive bacteria | ||||||
Staphyloccocus aureus ATCC6538 | 0.25/1 | 8/64 | >128/>128 | 2/2 | <0.125/<0.25 | 8/8 |
Bacillus cereus ATCC10876 | 2/2 | 64/64 | >128/>128 | 8/32 | <0.125/<0.25 | 1/1 |
Cells | ||
---|---|---|
Organisms | A549 | THP-1 |
Gram-negative bacteria | ||
Bordetella bronchiseptica 9.73H+ | 76.8 | 30.9 |
Escherichia coli ATCC25922 | 38.4 | 15.45 |
Pseudomonas aeruginosa PAO1 | 76.8 | 30.9 |
Burkholderia cenocepacia J2315 | 19.2 | 7.7 |
Pandorea apista DSM16535 | 38.4 | 15.45 |
Gram-positive bacteria | ||
Staphyloccocus aureus ATCC6538 | 153.6 | 61.8 |
Bacillus cereus ATCC10876 | 19.2 | 7.7 |
H-BDF | Tobramycin | Meropenem | Ceftazidime | |||||
---|---|---|---|---|---|---|---|---|
Clinical Isolates a | MIC (µg/mL) | MBC (µg/mL) | MIC (µg/mL) | MBC (µg/mL) | MIC (µg/mL) | MBC (µg/mL) | MIC (µg/mL) | MBC (µg/mL) |
Achromobacter xylosoxidans | ||||||||
A. xylosoxidans HNA 001 | 0.125 | 0.25 | R | nd | S | 8 | S | nd |
Burkholderia cenocepacia | ||||||||
B. cenocepacia CAMPA 669 | 0.25 | 2 | S | nd | S | nd | R | nd |
B. cenocepacia CAMPA 1533 | 4 | 16 | R | nd | R | 64 | S | 16 |
B. cenocepacia CAMPA 1194 | 2 | 4 | R | nd | R | nd | R | nd |
B. cenocepacia CAMPA 544 | 2 | 8 | R | nd | R | nd | S | 8 |
B. cenocepacia CAMPA 1771 | 8 | 16 | R | nd | I | 32 | R | nd |
B. cenocepacia CAMPA 817 | 2 | 8 | R | nd | R | nd | S | 8 |
B. cenocepacia CAMPA 548 | 2 | 4 | R | nd | R | nd | S | 8 |
B. cenocepacia CAMPA 825 (CBC 033) b | 4 | 16 | R | nd | I | nd | S | 32 |
B. cenocepacia CAMPA538 (CBC 035) b | 2 | 4 | R | nd | I | 16 | S | 16 |
B. cenocepacia CAMPA 817 | 2 | 8 | R | nd | R | nd | S | 16 |
B.cenocepacia CAMPA 531 | 1 | 4 | R | nd | S | nd | S | nd |
B.cenocepacia CAMPA 993 (CBC 024) b | 1 | 4 | R | nd | S | nd | S | nd |
B.cenocepacia HE001 | 4 | 64 | R | nd | R | nd | R | nd |
Burkholderia cepacia | ||||||||
B. cepacia CAMPA 545 | 4 | 16 | R | nd | R | nd | S | 16 |
B. cepacia CAMPA 233 (CBC 012) b | 2 | 4 | R | nd | S | 8 | S | 16 |
B. cepacia CAMPA 260 | 32 | nd | R | nd | R | 32 | R | nd |
B. cepacia CAMPA 914 | 32 | nd | R | nd | R | 32 | R | 64 |
B. cepacia CAMPA 886 | 32 | nd | R | nd | R | 32 | R | 128 |
B. cepacia CAMPA 998 | 32 | nd | R | nd | R | 64 | S | 32 |
B. cepacia CAMPA 1039 | 64 | nd | R | nd | R | 32 | R | nd |
B. cepacia CAMPA 853 (CBC 001) b | 32 | nd | R | nd | I | 64 | I | 64 |
B. cepacia CAMPA 860 (CBC 007) b | 64 | nd | R | nd | I | 64 | R | 64 |
B. cepacia CAMPA 660 | 4 | 8 | R | nd | S | 4 | R | nd |
B. cepacia CAMPA 721 (CBC 011) b | 2 | 32 | R | nd | S | 64 | R | nd |
Burkholderia contaminans | ||||||||
B. contaminans HNBC001 | 0.25 | 1 | R | nd | R | nd | S | nd |
Burkholderia multivorans | ||||||||
B. multivorans CAMPA 661(CBC 015) b | 2 | 4 | R | nd | S | 4 | S | 8 |
B. multivorans CAMPA 1530 | 2 | 8 | R | nd | R | nd | S | 4 |
B. multivorans CAMPA 647 (CBC 017) b | 4 | 4 | R | nd | S | 4 | S | 8 |
B. multivorans CAMPA 653 (CBC 018) b | 2 | 8 | R | nd | S | 4 | S | 8 |
B. multivorans CAMPA 623(CBC 019) b | 2 | 8 | R | nd | S | 8 | R | nd |
B. multivorans CAMPA 832 (CBC 020) b | 4 | 16 | R | nd | S | 32 | R | nd |
B. multivorans CAMPA 987 (CBC 021) b | 2 | 4 | R | nd | S | 8 | R | nd |
B. multivorans CAMPA 997 (CBC 022) b | 4 | 8 | R | nd | S | 8 | R | nd |
Burkholderia seminalis | ||||||||
B. seminalis CAMPA 231 | 32 | nd | R | nd | I | nd | R | 32 |
B. seminalis CAMPA 261 (CBC 039) b | 32 | nd | R | nd | S | 16 | S | 16 |
B. seminalis CAMPA 475 (CBC 040) b | 4 | 8 | R | nd | I | nd | R | nd |
B. seminalis CAMPA 227 | 1 | 8 | R | nd | R | nd | R | nd |
Burkholderia vietnamiensis | ||||||||
B. vietnamiensis CAMPA 992 (CBC 038) b | 32 | nd | R | nd | S | 8 | S | 16 |
Staphylococcus aureus | ||||||||
S. aureus CAMPA 1909 | 2 | 16 | 128 | nd | >128 | nd | >128 | nd |
S. aureus CAMPA 1908 | 1 | 4 | 32 | >128 | >128 | nd | >128 | nd |
Stenotrophomonas maltophilia | ||||||||
S. maltophilia CAMPA 1911 | 2 | 16 | >128 | nd | >128 | nd | >128 | nd |
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Saeed, A.; Bosch, A.; Bettiol, M.; Nossa González, D.L.; Erben, M.F.; Lamberti, Y. Novel Guanidine Compound against Multidrug-Resistant Cystic Fibrosis-Associated Bacterial Species. Molecules 2018, 23, 1158. https://doi.org/10.3390/molecules23051158
Saeed A, Bosch A, Bettiol M, Nossa González DL, Erben MF, Lamberti Y. Novel Guanidine Compound against Multidrug-Resistant Cystic Fibrosis-Associated Bacterial Species. Molecules. 2018; 23(5):1158. https://doi.org/10.3390/molecules23051158
Chicago/Turabian StyleSaeed, Aamer, Alejandra Bosch, Marisa Bettiol, Diana L. Nossa González, Mauricio Federico Erben, and Yanina Lamberti. 2018. "Novel Guanidine Compound against Multidrug-Resistant Cystic Fibrosis-Associated Bacterial Species" Molecules 23, no. 5: 1158. https://doi.org/10.3390/molecules23051158