In Vitro and In Silico Analysis of Differential Antibacterial Activity of Pomegranate Polyphenols Against Gram-Positive and Gram-Negative Bacteria
Abstract
1. Introduction
2. Results
2.1. Chemical Composition of Pomegranate Peel Extract
2.2. In Vitro Antimicrobial Activity Results
2.3. Molecular Docking Study Results
2.4. Results of Transport Studies Through Porin Channels
3. Discussion
3.1. Chemical Analysis
3.2. Differential Antimicrobial Activity
3.3. Mechanism of Action Based on Molecular Docking Studies
4. Materials and Methods
4.1. Plant Material and Extract Preparation
4.2. Chemical Analysis of Polyphenolic Compounds
4.3. In Vitro Antimicrobial Activity
4.4. Molecular Docking Studies
4.5. Transport Studies Through Porin Channels
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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No. | RT (280 nm) | MW | [M − H] − (m/z) (100 V) | MS Data (m/z) (250V) | Compound Name | Concentration (mg/g Dry Extract) |
---|---|---|---|---|---|---|
1 | 3235 | 482 | 481 | 275, 301 | HHDP-hexoside | 4.58 ± 0.00 |
2 | 3736 | 782 | 781 | 601, 721 | Punicalin isomer α (4,6-gallagyl-glucose) | 10.44 ± 0.00 |
3 | 3933 | 782 | 781 | 601, 721 | Punicalin isomer β | 12.14 ± 0.00 |
4 | 5045 | 784 | 783 | 481, 301 | Penduculagin I isomer (bis-HHDP-hexoside) | 12.5 ± 0.00 |
5 | 8329 | 1084 | 1083 | 781, 601 | Punicalagin isomer α (HHDP-gallagyl-glicoside) | 311.28 ± 0.23 |
6 | 11,064 | 1084 | 1083 | 781, 601 | Punicalagin isomer β (HHDP-gallagyl-glucoside) | 312.63 ± 0.28 |
7 | 13,795 | 634 | 633 | 463, 301 | Galloyl–HHDP hexoside | 5.71 ± 0.00 |
8 | 15,373 | 786 | 785 | 755, 301 | Tellimagrandin I | 2.74 ± 0.00 |
9 | 17,343 | 464 | 463 | 301, 463 | Ellagic acid-hexoside | 6.01 ± 0.01 |
10 | 25,177 | 302 | 301 | 301 | Ellagic acid | 26.54 ± 0.03 |
Isolate Code | Species | Penicillin | Ampicillin | Amoxicillin/Clavulanic Acid | Cefaclor | Ceftriaxone | Erythromycin | Gentamicin | Ciprofloxacin | Vancomycin | Cefuroxime | Cefotaxime | Ceftazidime | Cefepime | Amikacin | Trimethoprim/Sulfamethoxazole | Piperacillin | Piperacillin/Tazobactam | Imipenem | Meropenem |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | S. aureus | S | S | S | S | S | S | S | S | S | - | - | - | - | - | - | - | - | - | - |
2 | R | R | S | S | S | S | S | R | S | - | - | - | - | - | - | - | - | - | - | |
3 | S | S | S | S | S | S | S | S | S | - | - | - | - | - | - | - | - | - | - | |
4 | S | S | S | S | S | R | S | S | S | - | - | - | - | - | - | - | - | - | - | |
5 | S | S | S | S | S | S | R | S | S | - | - | - | - | - | - | - | - | - | - | |
6 | S | S | S | S | S | S | S | S | S | - | - | - | - | - | - | - | - | - | - | |
1 | E. coli | - | R | R | - | S | - | S | S | - | S | S | S | S | S | S | R | S | S | S |
2 | - | R | S | - | S | - | S | S | - | S | S | S | S | S | S | R | S | S | S | |
3 | - | R | S | - | S | - | S | S | - | S | S | S | S | S | S | R | S | S | S | |
4 | - | S | S | - | S | - | S | R | - | S | S | S | S | S | R | R | S | S | S | |
5 | - | R | R | - | S | - | R | S | - | S | S | S | S | S | R | R | S | S | S |
Isolate | PoPEx | Punicalin | Punicalagin | Pedunculagin | Gallic Acid | Ellagic Acid |
---|---|---|---|---|---|---|
1 | 31.25 ± 0.00 | 62.50 ± 0.00 | 15.62 ± 0.00 | 500.00 ± 0.00 | 125.00 ± 0.00 | 250.00 ± 0.00 |
2 | 31.25 ± 0.00 | 62.50 ± 0.00 | 20.83 ± 7.37 | >500.00 | 125.00 ± 0.00 | 250.00 ± 0.00 |
3 | 20.83 ± 7.37 | 62.50 ± 0.00 | 15.62 ± 0.00 | 500.00 ± 0.00 | 125.00 ± 0.00 | 250.00 ± 0.00 |
4 | 31.25 ± 0.00 | 52.08 ± 17.73 | 15.62 ± 0.00 | 500.00 ± 0.00 | 125.00 ± 0.00 | 250.00 ± 0.00 |
5 | 31.25 ± 0.00 | 62.50 ± 0.00 | 31.25 ± 0.00 | 416.66 ± 117.85 | 125.00 ± 0.00 | 250.00 ± 0.00 |
6 | 20.83 ± 7.37 | 62.50 ± 0.00 | 15.62 ± 0.00 | >500.00 | 166.67 ± 58.93 | 250.00 ± 0.00 |
Isolate | PoPEx | Punicalin | Punicalagin | Pedunculagin | Gallic Acid | Ellagic Acid |
---|---|---|---|---|---|---|
1 | 250.00 ± 0.00 | 500.00 ± 0.00 | 250.00 ± 0.00 | >500 | 125.00 ± 0.00 | 208.33 ± 58.93 |
2 | 250.00 ± 0.00 | 500.00 ± 0.00 | 333.33 ± 117.85 | >500 | 125.00 ± 0.00 | 250.00 ± 0.00 |
3 | 250.00 ± 0.00 | 500.00 ± 0.00 | 250.00 ± 0.00 | 500.00 ± 0.00 | 125.00 ± 0.00 | 250.00 ± 0.00 |
4 | 208.33 ± 58.93 | 500.00 ± 0.00 | 250.00 ± 0.00 | >500 | 125.00 ± 0.00 | 125.00 ± 0.00 |
5 | 250.00 ± 0.00 | 416.67 ± 117.85 | 250.00 ± 0.00 | >500 | 125.00 ± 0.00 | 250.00 ± 0.00 |
Ligand | Target Protein | GP Binding Energy (kcal/mol) | GP Interactions | GN Binding Energy (kcal/mol) | GN Interactions |
---|---|---|---|---|---|
Punicalin | PBPs * | −8.878 | Asn 111, Asp 128, Gly 135, His 311 | −6.253 | Ser 429, Asn 450, Glu 623, Val 632, Val 658, Pro 659, Pro 660 |
Punicalagin | −9.096 | Ser 149, Thr 216, Pro 258, Val 277, Asp 295, Tyr 373 | −3.18 | Lys 427, Arg 428, Ser 429, Asn 450, Asp 519, Glu 623, Pro 659, Pro 660 | |
Pedunculagin | −8.659 | Tyr 255, Asn 260, Glu 263, Phe 371, Asn 377, Asn 381 | −6.658 | Thr 426, Asn 432, Asp 519, Thr 621, Glu 623, Pro 659 | |
Gallic a. | −5.593 | Thr 444, Asn 464, Tyr 519, Glu 602 | −6.074 | Pro 660 | |
Ellagic a. | −7.654 | Lys 215, Val 217, Lys 218, Asp 221, Pro 370, Gly 374, Glu 379 | −9.01 | Ser 392, Ser 448, Asn 450, Thr 603, Gly 620, Pro 660 | |
Punicalin | MurA ** | −8.951 | Pro 125, Glu 127, Phe 164, Thr 329, Glu 332 | −8.841 | Lys 46, Leu 47, Asp 51, Asp 396, Ile 402, Arg 415 |
Punicalagin | −7.765 | Asp 163, Phe 164, Glu 332, Arg 353 | −8.738 | Lys 46, Leu 47, Asp 51, Asp 396, Arg 401, Arg 415, Lys 417 | |
Pedunculagin | −8.434 | Asp 2, Glu 52, Leu 395, Asp 399, Arg 400, Arg 418, Asn 420 | −8.484 | Lys 160, Val 161, Thr 326, Glu 329 | |
Gallic a. | −6.325 | Asp 308, Leu 373, Arg 400 | −5.258 | Pro 9, Ser 245, Arg 246, Ile 382 | |
Ellagic a. | −8.788 | Lys 22, Cys 119, Arg 124, Asp 308, Arg 334, Asp 372, Leu 373, Arg 400 | −7.034 | Leu 47, Tyr 399, Ile 402, Glu 403, Arg 401, Arg 415 | |
Punicalin | FtsZ *** | −7.803 | Glu 185, Asn 188, Gln 192, Lys 243, Ser 246, Pro 248 | −9.154 | Asn 24, Asp 45, Thr 65, Arg 142 |
Punicalagin | −8.648 | Glu 185, Gly 229, Val 230, Lys 243, Ser 246, Pro 248 | −10.031 | Gly 20, Asn 43, Asp 45, Ala 48, Thr 65, Gly 67, Ala 72, Lys 141, Arg 142 | |
Pedunculagin | −8.551 | Asn 44, Asp 46, Gln 48, Ala 49 | −8.658 | Gly 20, Asn 24, Thr 44, Asp 45, Gly 71, Thr 108 | |
Gallic a. | −5.426 | Asp 199, Leu 200, Val 203, Val 297, Asn 299 | −5.347 | Gln 194, Ser 227 | |
Ellagic a. | −8.439 | Asp 199, Leu 200, Val 203, Thr 265, Val 297, Asn 299, Val 307 | −7.607 | Asp 187, Lys 190, Gln 194, Ser 227, Thr 309 |
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Suručić, R.; Travar, M.; Kundaković Vasović, T.; Radović Selgrad, J.; Suručić, L.; Momčilović, M.; Stojiljković, M.P.; Škrbić, R. In Vitro and In Silico Analysis of Differential Antibacterial Activity of Pomegranate Polyphenols Against Gram-Positive and Gram-Negative Bacteria. Antibiotics 2025, 14, 912. https://doi.org/10.3390/antibiotics14090912
Suručić R, Travar M, Kundaković Vasović T, Radović Selgrad J, Suručić L, Momčilović M, Stojiljković MP, Škrbić R. In Vitro and In Silico Analysis of Differential Antibacterial Activity of Pomegranate Polyphenols Against Gram-Positive and Gram-Negative Bacteria. Antibiotics. 2025; 14(9):912. https://doi.org/10.3390/antibiotics14090912
Chicago/Turabian StyleSuručić, Relja, Maja Travar, Tatjana Kundaković Vasović, Jelena Radović Selgrad, Ljiljana Suručić, Milan Momčilović, Miloš P. Stojiljković, and Ranko Škrbić. 2025. "In Vitro and In Silico Analysis of Differential Antibacterial Activity of Pomegranate Polyphenols Against Gram-Positive and Gram-Negative Bacteria" Antibiotics 14, no. 9: 912. https://doi.org/10.3390/antibiotics14090912
APA StyleSuručić, R., Travar, M., Kundaković Vasović, T., Radović Selgrad, J., Suručić, L., Momčilović, M., Stojiljković, M. P., & Škrbić, R. (2025). In Vitro and In Silico Analysis of Differential Antibacterial Activity of Pomegranate Polyphenols Against Gram-Positive and Gram-Negative Bacteria. Antibiotics, 14(9), 912. https://doi.org/10.3390/antibiotics14090912