Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Antibiofilm assay of fluoroquinolones and PPI’s_
| Sample | Staphylococcus aureus | Staphylococcus epidermidis |
|---|---|---|
| Ciprofloxacina | 67 ± 1.23% | 65 ± 2.1% |
| CIP-OMP | 78 ± 2.1% | 75 ± 0.48% |
| LEVb | 74 ± 1.83% | 68 ± 1.4% |
| LEV-OMP | 82 ± 2.4% | 76 ± 1.87% |
Docking score, H and non H-bonding interactions of tested PPI’s_
| Compound | Binding free energy ΔG (kJ mol−1) | Pose rank | No. of H bonds | H bond interaction residues | Other interaction residues |
|---|---|---|---|---|---|
| 4BXI | |||||
| Dexlansoprazole | –6.1 | 4 | 2 | Lys289, Lys294 | Glu286, Leu288, Ile313, Ile297, Ile301, Ile285 |
| Esomeprazole | –5.8 | 1 | 1 | Lys401 | Phe386, His379, Ile378, IL3375, Ile416, Phe382 |
| Lansoprazole | –6.5 | 2 | 1 | Asp405 | Lys401, Ala404, Asp408, Val410, Ala407, Leu411, Leu412, Leu 397 |
| Omeprazole | –5.4 | 7 | 2 | Leu412, Thr414 | Val410, Asp405, Ala404, Phe382, Leu397, Lys397, Lys401, Leu411 |
| Pantoprazole | –6.0 | 1 | 1 | His 379 | Phe386, Lys401, Phe382, Ile378, Phe421, Ile416 |
| Rabeprazole | –5.7 | 2 | 2 | Thr414, Lys401 | Phe382, Gln383, Phe386, Leu412, Asp413 |
| 3QP1 | |||||
| Dexlansoprazole | –5.7 | 8 | 3 | Glu112, Ser137, Thr131 | Lys 124, Asn116, Phe 115, Ile127, Gly136, Arg159 |
| Esomeprazole | –5.9 | 3 | 4 | Gln95, Arg101, Leu72, Asn64 | Ala94, Ile69, Leu100, Gln70, Arg71, Gln68 |
| Lansoprazole | –6.2 | 1 | 1 | Met30 | Glu26, Ile34, Glu39, His33, His29 |
| Omeprazole | –6.0 | 2 | 4 | Arg101, Leu72, Gln95, Asn64 | Gln68, Ile69, Leu100, Ala94, Gln70, Arg71, |
| Pantoprazole | –6.2 | 1 | 4 | Leu72, Arg101, Asn64, Gln95 | Gln70, Ala94, Ile69, Leu100, |
| Rabeprazole | 2 | 3 | Arg101, Asn64, Gln95 | Gln66, Ile69, Leu72, Leu100, Ala94, Gln68 | |
Determination of minimum inhibitory concentration MIC (μg/ml) of tested compounds_
| Sample | Staphylococcus epidermidis | Staphylococcus aureus |
|---|---|---|
| Omeprazole | > 64 | 3.9 |
| Esomeprazole | > 64 | > 64 |
| Pantoprazole | > 64 | > 64 |
| Dexlansoprazole | > 64 | > 64 |
| Lansoprazole | > 64 | > 64 |
| Rabeprazole | > 64 | > 64 |
| Ofloxacin | 3.9 | 1.9 |
| Ofloxacin/Omeprazole | 3.9 | 3.9 |
| Ofloxacin/Esomeprazole | 3.9 | 3.9 |
| Ofloxacin/Pantoprazole | 3.9 | 3.9 |
| Ofloxacin/Dexlansoprazole | 3.9 | 3.9 |
| Ofloxacin/Lansoprazole | 3.9 | 3.9 |
| Ofloxacin/Rabeprazole | 3.9 | 3.9 |
| Norfloxacin | 7.8 | 3.9 |
| Norfloxacin/Omeprazole | 3.9 | 3.9 |
| Norfloxacin/Esomeprazole | 3.9 | 3.9 |
| Norfloxacin/Pantoprazole | 3.9 | 3.9 |
| Norfloxacin/Dexlansoprazole | 3.9 | 3.9 |
| Norfloxacin/Lansoprazole | 3.9 | 3.9 |
| Norfloxacin/Rabeprazole | 3.9 | 3.9 |
| Moxifloxacin | 3.9 | 3.9 |
| Moxifloxacin/Omeprazole | 3.9 | 3.9 |
| Moxifloxacin/Esomeprazole | 3.9 | 3.9 |
| Moxifloxacin/Pantoprazole | 3.9 | 3.9 |
| Moxifloxacin/Dexlansoprazole | 3.9 | 3.9 |
| Moxifloxacin/Lansoprazole | 3.9 | 3.9 |
| Moxifloxacin/Rabeprazole | 3.9 | 3.9 |
| Ciprofloxacin | 0.24 | 0.24 |
| Ciprofloxacin/Omeprazole | 0.12 | 0.12 |
| Ciprofloxacin/Esomeprazole | 0.24 | 0.24 |
| Ciprofloxacin/Pantoprazole | 0.12 | 0.24 |
| Ciprofloxacin/Dexlansoprazole | 0.24 | 0.24 |
| Ciprofloxacin/Lansoprazole | 0.24 | 0.24 |
| Ciprofloxacin/Rabeprazole | 0.24 | 0.24 |
| Levofloxacin | 1.2 | 1.2 |
| Levofloxacin/Omeprazole | 0.12 | 0.48 |
| Levofloxacin/Esomeprazole | 0.24 | 15.6 |
| Levofloxacin/Pantoprazole | 0.24 | 31.25 |
| Levofloxacin/Dexlansoprazole | 0.48 | 31.2 |
| Levofloxacin/Lansoprazole | 0.24 | 31.2 |
| Levofloxacin/Rabeprazole | 0.24 | 31.2 |
Docking score, H and non H-bonding interactions of fluoroquinolones compounds_
| Compound | Binding free energy ΔG (kJ mol−1) | Pose rank | No. of H bonds | H bond interaction residues | Other interaction residues |
|---|---|---|---|---|---|
| 4BXI | |||||
| Ciprofloxacin | –5.7 | 3 | 2 | Ile416, His379 | Phe421, Thr414, Ile415, Phe382, Ile378 |
| Levofloxacin | –5.7 | 1 | 2 | Ile416, His379 | Phe421, Ile378, Phe382, Ile415, Thr414, |
| Moxifloxacin | –6.4 | 3 | 2 | Ala404, Thr414 | Asp 413, Lys401, Leu412, Asp405, Val410, Leu411 |
| Norfloxacin | –6.3 | 2 | 3 | His379, Ile416 | Ile378, Phe382, Thr414, Ile415, Phe421 |
| Ofloxacin | –6.6 | 4 | 2 | Arg331, Leu395 | Asn339, Glu384, Leu381, Glu342, Ile335, Asp338 |
| 3QP1 | |||||
| Ciprofloxacin | –5.6 | 7 | 3 | Ser53, Glu54, Ala57 | Pro52, Arg159, Arg163, Gly158, Arg55 |
| Levofloxacin | –6.5 | 2 | 2 | Gly105, Arg10 | Met9, Pro176, Gln180, His177, Ala144 |
| Moxifloxacin | –6.3 | 2 | 3 | Gly136, Ser137, Arg159 | Glu160, Pro52, Ala157, Arg55, Met135, Gly134, |
| Norfloxacin | –5.4 | 6 | 3 | Arg159, Ser137, Gly134 | Arg55, Glu54, Ser53, Pro52, Gly158, |
| Ofloxacin | –6.3 | 2 | 3 | Arg159, Gly136, Ser137 | Gly134, Arg55, Gly158, Ala157, Pro52, Glu54 |
Determination of antiquorum sensing activity of tested compounds_
| Sample | Anti QS (mm) | % Violacine inhibition |
|---|---|---|
| Omeprazole | 12 ± 0.12 | 56 ± 1.4 |
| Esomeprazole | 2 ± 0.11 | 0 |
| Pantoprazole | 0 | 0 |
| Dexlansoprazole | 2 ± 0.00 | 0 |
| Lansoprazole | 0 | 0 |
| Rabeprazole | 0 | 0 |
| Ofloxacin | 14 ± 1.00 | 65 ± 1.2 |
| Ofloxacin/Omeprazole | 19 ± 1.1 | 74 ± 1.24 |
| Ofloxacin/Esomeprazole | 18 ± 1.2 | 65 ± 0.56 |
| Ofloxacin/Pantoprazole | 16 ± 0.14 | 65 ± 1.45 |
| Ofloxacin/Dexlansoprazole | 18 ± 0.12 | 70 ± 1.41 |
| Ofloxacin/Lansoprazole | 19 ± 0.25 | 69 ± 1.6 |
| Ofloxacin/Rabeprazole | 19 ± 0.25 | 68 ± 1.4 |
| Moxifloxacin | 18 ± 1.1 | 62 ± 1.2 |
| Moxifloxacin/Omeprazole | 19 ± 0.56 | 70 ± 1.02 |
| Moxifloxacin/Esomeprazole | 18 ± 0.42 | 68 ± 0.78 |
| Moxifloxacin/Pantoprazole | 18 ± 0.00 | 66 ± 0.63 |
| Moxifloxacin/Dexlansoprazole | 18 ± 0.47 | 65 ± 1.6 |
| Moxifloxacin/Lansoprazole | 20 ± 0.63 | 72 ± 2.2 |
| Moxifloxacin/Rabeprazole | 20 ± 0.00 | 70 ± 1.7 |
| Norfloxacin | 18 ± 0.23 | 72 ± 0.63 |
| Norfloxacin/Omeprazole | 18 ± 0.45 | 68 ± 2.4 |
| Norfloxacin/Esomeprazole | 18 ± 0.63 | 65 ± 1.7 |
| Norfloxacin/Pantoprazole | 20 ± 1.1 | 68 ± 1.3 |
| Norfloxacin/Dexlansoprazole | 18 ± 0.63 | 70 ± 1.21 |
| Norfloxacin/Lansoprazole | 18 ± 0.42 | 72 ± 1.36 |
| Norfloxacin/Rabeprazole | 18 ± 0.12 | 70 ± 1.24 |
| Ciprofloxacin | 14 ± 0.63 | 60 ± 1.64 |
| Ciprofloxacin/Omeprazole | 19 ± 1.1 | 75 ± 0.46 |
| Ciprofloxacin/Dexomeprazole | 16 ± 1.3 | 68 ± 1.27 |
| Ciprofloxacin/Pantoprazole | 19 ± 1.1 | 76 ± 0.61 |
| Ciprofloxacin/Omeprazole | 16 ± 0.45 | 66 ± 2.5 |
| Ciprofloxacin/Esomeprazole | 19 ± 0.62 | 76 ± 1.4 |
| Levofloxacin | 20 ± 0.63 | 72 ± 1.26 |
| Levofloxacin/Omeprazole | 20 ± 0.45 | 76 ± 1.09 |
| Levofloxacin/Esomeprazole | 20 ± 0.25 | 70 ± 1.6 |
| Levofloxacin/Pantoprazole | 20 ± 0.13 | 74 ± 0.23 |
| Levofloxacin/Dexlansoprazole | 20 ± 0.45 | 72 ± 1.56 |
| Levofloxacin/Lansoprazole | 20 ± 0.12 | 74 ± 1.20 |
| Levofloxacin/Rabeprazole | 20 ± 0.63 | 76 ± 1.36 |