MOLECULAR DOCKING AND BIOLOGICAL EVALUATION OF ACACIA FERRUGINEA AND ITS ACTIVE PRINCIPLE, SEVERIN, AGAINST CHROMOBACTERIUM VIOLACEUMHTML Full Text
MOLECULAR DOCKING AND BIOLOGICAL EVALUATION OF ACACIA FERRUGINEA AND ITS ACTIVE PRINCIPLE, SEVERIN, AGAINST CHROMOBACTERIUM VIOLACEUM
M. Jeevitha *, Vinothkannan Ravichandran and Shubashini K. Sripathi
Department of Chemistry, Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore, Tamil Nadu, India.
ABSTRACT: Misuse and overuse of antibiotics, multi drug resistance bacterial strains have emerged as silent pandemic. Lately, antibiofilm treatment approach using natural compounds have ascended as an alternate strategy to overcome the issue. In this study, the inhibitory effect of bark and leaf extracts of Acacia ferruginea against a model bacterium, Chromobacterium violaceum was evaluated. Results revealed that A. ferruginea extract has a significant inhibitory effect on virulence determinants (biofilm and violacein productions) with no effect on growth.19 unrelated compounds were identiﬁed from GC-MS analysis. In molecular docking studies, six hits were found to have potential interactions with CviR, a quorum sensing regulatory protein. One of the major hits, severin, formed H-bond with Ser155 and Asp 97 with highest Gscore -8.862 when compared to the standard ligand, C6HSL (-7.052). Our data showed that the leaf and bark ethanolic extracts of A. ferruginea will be a promising synergetic remedy against bacterial infections from natural sources by curbing quorum sensing.
Keywords: Acacia ferruginea, Quorum sensing, GC-MS, Chromobacterium violaceum, Medicinal Plants, Severin
INTRODUCTION: The prevalence in multidrug-resistant pathogenic bacteria is steadily rising across the world, which is of primary concern for the health professionals and the Infectious Diseases Society of America (IDSA) has acknowledged antimicrobial resistance as one of the greatest hazards to the public welfare globally. Pathogens have evolved to become resistant due to increased, often excessive and improper usage of antibiotics and they became uncontainable superbugs 1, 2. To combat these super bugs, it is essential to identify and evaluate alternative strategies.
Many bacteria use quorum sensing (QS) as a cell-to-cell communication mechanism to manage their biofilm and pathogenic factors and is found that interfering with QS is a novel approach to combat bacterial pathogen city without affecting their growth of MDR pathogens 3, 4. In both Gram-negative and Gram-positive bacteria, QS is controlled by signal molecules termed auto inducers (AIs) that are released, sensed, and responded to regulate phenotypic features like as bioluminescence, biofilm formation, antibiotic synthesis and pathogenicity, based on cell density.
Gram-negative bacteria produce a small signalling molecule called N-acyl-L-homoserine lactones (AHLs) whereas in Gram-positive bacteria small peptides act as AIs 5, 6. Chromobacterium violaceum, a Gram-negative bacterium is known to produce violacein (a purple pigment), under the control of QS system. Violacein has dimeric structure which is comprised of oxindole, 5-hydroxyindole and 2-pyyrolidone subunits and is regulated vioB, vioD, vioA and vioC genes 7, 8. Quorum sensing controls wide range of behaviours in the Chromobacterium violaceum which uses a quorum-sensing system (LuxIR-type) to sense and react based on bacterial cell density changes. The autoinducer C6-homoserine lactone (C6-HSL) is encoded by CviI and the CviR protein is encoded by CviRgenes 9. QS system controls various phenotypes such as biofilm formation, violacein production, elastase production, chitinolytic activity in C. violaceum 10, 11, 12, 13.
As a well-known bio-monitor strain for QS system, C. violaceum have been commonly used to discover anti-QS compounds that can obstruct the QS pathway which can be obviously seen as a reduction in violacein pigment possibly by inhibiting CviR, a QS regulator protein 14.
Medicinal plants occupy a significant role in the treatment of infections since they possess enormous bioactive substances with a diverse spectrum of bioactivities (antifungal, antibacterial, anti-inflammatory behaviors etc.,). Numerous studies tend to focus herbal plants that play a crucial role in the treatment and management of various diseases owing to their limited side effects, efficacy, convenience and cost effectiveness. Acacia species are multipurpose trees and are a rare natural source in the conventional medicine systems to heal a diverse range of diseases.
And one such Acacia species is A. ferruginea DC., which belongs to Mimosiaceae family. In folk medicine, it has been commonly used for the management of inflammation, pain, cancer cure and to treat numerous ailments such as hemorrhage, leprosy, irritable bowel syndrome 15, 16, 17.
The methanol extracts of aerial parts of A. ferruginea is said to be protective against cyclophosphamide induced toxicities, due to higher antioxidant capability 18.
Here, we aimed to study the anti-QS properties of A. ferruginea DC., extracts using C. violaceum and to identify the active constituents by GC-MS studies. Further, we also studied the possible interactions of these active constituents with CviR by molecular docking.
MATERIALS AND METHODS:
Plant Collection and Extraction: The leaves and bark of Acacia ferruginea were collected from Nalligoundanpalayam, Avinashi, Tamil Nadu during September 2018. The plant was authenticated by Dr. R. Manikandan, Scientist D, Botanical Survey of India, Coimbatore (BSI/SRC/5/23/2018/Tech/2080). The leaves and bark were cleaned thoroughly and dried under shade. The dried samples were pulverized and 170g of each powder was extracted with hexane, ethyl acetate, ethanol, hydro ethanol (90:10 ethanol-water) and distilled water in a soxhlet apparatus for 6 h. The extracts were further concentrated under reduced pressure. The aqueous extracts were lyophilized and stored at 4°C until further use.
Biofilm Inhibition: Microtitre plate assay was employed to assess the effect of Acacia ferruginea on biofilm formation 46. To 1mL of freshly prepared LB medium, the overnight culture of C. violaceum (0.4 OD at 600nm) was added in the presence and the absence of Acacia ferruginea bark ethanolic extract (BEE) and leaf ethanolic extract (LEE) of varying concentrations (100, 200, 300, 400, 500 μg/ml). Bacteria were grown without agitation for 24h at 30ºC. After incubation, the supernatant was discarded, and the phosphate-buffered saline (PBS -pH 7.4) was added to the wells and stained with 200 μl of 0.4% crystal violet and incubated for 15 min. The solution was discarded after 15 minutes and to solubilize the crystal violet 200 μL of 95% ethanol was added. The absorbance was read in a microplate reader (Infinite M200, Tecan) at OD 470 nm and the biofilm was quantified.
Growth Curve Analysis: The index of growth inhibition was noted by measuring the difference between the absorbance of the microwell cultures at zero time (at inoculation) and the absorbance after the incubation period. Analysing the growth of the bacteria is an important phenomenon to differentiate the anti-biotic activity from anti-quorum sensing activity. To confirm the anti-QS activity of the phytochemicals, the growth curve assay of C. violaceum was performed in the presence and absence of BEE, LEE. Overnight culture of the bacteria (1%; A600 nm=0.4) was inoculated in a 250-mL Erlenmeyer flask containing 50 mL of LB broth supplemented with different concentrations. The flasks were incubated at 30 °C and 180 rpm in a rotary shaker. The cell density was measured by UV-Vis spectro-photometer (UV-1800; Shimadzu) at 1-hour intervals up to 20 h. The control was the bacteria without the treatment with phytochemicals 47.
Violacein Quantification: Violacein pigment was quantified by flask incubation assay 48. Briefly, C. violaceum (CV12472) was incubated for 16-18 h. It was then inoculated to Erlenmeyer flasks containing 20 mL LB which was supplemented with extracts (BEE and LEE) of varying concentrations (100, 200, 300, 400, 500 μg/mL). The flasks were incubated at 30°C, with shaking at 150 rpm for 24 h in a shaker incubator. To 1.5 mL Eppendorf tube, 1 mL of each culture sample was transferred and centrifuged at 13000 rpm (10 min) and thereby violacein (insoluble part) was precipitated. 1 mL of DMSO was added to the pellet after discarding the culture supernatant. It was vortexed vigorously for 30s, to completely solubilize violacein and centrifuged was at 13000 rpm for 10 min to remove the cells. Violacein-containing supernatants (200 μL) was transferred to 96-well flat-bottomed microplate and the absorbance was read at 585 nm in a microplate reader (Infinite M200, Tecan).
GC-MS Analysis: The hexane extract and hydroethanolic extract of A. ferruginea were subjected to GC-MS analysis using a PerkinElmer Clarus 680 GC-MS system for predicting the chemical constituents. The oven program was kept at the temperature of 60 °C for 2 min and ramped at 10 °C/min to 300 °C (hold for 6min), Helium (1mL/min) was used as carriergas. Column used was Elite-5MS (30.0m, 0.25mmID, 250μm df) and the injector temperature (280 °C). One microlitre of sample dissolved in ethanol was injected into the system. The compounds were identiﬁed by comparison of the mass spectrum of the corresponding GC peaks with that in the NIST (National Institute of Standard and Technology) database.
Docking Studies: Docking studies was performed using Schrodinger software (Maestro v10.6,) Glide module. All the ligands identified by GC-MS were tested for their ability to interact with CviR protein. Using LigPrep module the energy saving 3D ligand ﬁle was prepared 49. From the Protein Data Bank (PDB: 3QP1) three-dimensional structure of CviR protein was obtained and the coordinates of the CviR structure have been prepared. In the center of both grid boxes using the C6HSL, the native ligand grid files were created and the active site residues are noted (Asp 97, Ser 155, Trp 84 and Tyr 80). Hits with more H-bonds and less GScore and were further assessed.
RESULTS AND DISCUSSION: The ethanolic extract of A. ferruginea bark and leaves were found to inhibit the biofilm and violacein pigment significantly without affecting the growth. From the GC-MS study 19 different compounds were found. A potential interaction with CviR with good Gscore was reported from the molecular docking studies from six hits.
Biofilm Inhibition: Since, biofilm is also one of the key determinants regulated by quorum sensing and plays a vital role in pathogenicity and drug resistance, it is essential to assess the extracts' efficiency against quorum sensing governed phenotypes, particularly in C. violaceum. All the tested extracts reduced the key pathogenic factor biofilm formation in concentration dependent manner at various concentrations (100, 200, 300, 400 and 500 µg/mL. Especially, ethanol extract of A. ferruginea leaves and bark has significant effect with 69.81% and 67.84% respectively, when supplied with 500μg/mL of leaf ethanolic extract (LEE) and Bark ethanolic extract (BEE) Fig. 1. At 200 and 400 µl the biofilm inhibition of bark extract was found to be higher, whereas the inhibition was found to be comparatively less for all other concentrations when compared to leaf extract.
FIG. 1: BIOFILM INHIBITION ANALYSIS OF BARK AND LEAF ETHANOLIC EXTRACT OF A. FERRUGINEA
Growth Curve Analysis: The growth of these plant extracts was examined to distinguish their quorum sensing inhibition activity from antibiotic activity. As there is no significant growth inhibition was found in both the BEE and LEE of A. ferruginea, we can infer that they possess quorum sensing inhibitors rather than antibiotics Fig. 2.
FIG. 2: GROWTH CURVE ANALYSIS OF BARK AND LEAF ETHANOLIC EXTRACT OF A. FERRUGINEA
FIG. 3: EFFECT OF ETHANOLIC EXTRACTS OF BARK AND LEAVES OF A. FERRUGINEA IN VIOLACEIN INHIBITION
Violacein Quantification: C. violaceum produces “Violacein” (purple pigment) that is controlled by QS mechanism (via vioABCDE operon). The violacein pigment was suppressed in a concentration-dependent manner by an ethanolic extract of the leaves and bark. The leaf extract was more likely to inhibit violacein than the bark extract. The inhibition percentage of violacein in the leaf extract was higher (62.84 %) at a concentration of 500 g/mL than in the bark extract. (49.81%) Fig. 3.
GC-MS Analysis: From GC-MS analysis totally 10 probable compounds were identified from leaves Table 1A and 9 compounds from bark Table 1B. The GC/MS chromatograms of ethanol extracts of A. ferruginea bark and leaves are shown in the Fig. 4A and 4B respectively. 2R-acetoxymethyl - 1, 3, 5-trimethyl - 4c - (3-methyl-2-buten-1-yl)-1c-cyclohexanol (27.70%), from bark extract showed highest area percentage followed by 1-naphthalenepropanol,. alpha.-ethyldecahydro – 5 - (hydroxymethyl) -.alpha., 2, 5, 5, 8a-pentamethyl with (23.96%),1,3,3-trimethyl-2-hydroxymethyl-3, 3-dimethyl - 4-(3-methylbut-2-enyl)-cyclohexene with (18.78%) and least area percentage of about (1.34%) for Germacra-1(10),11(13)-dien-12-oic acid, 4,5-alpha-epoxy-6-beta-hydro (Parthenolide) was observed.
The area % of compounds from leaf extracts were observed as 25.83% for 6-dimethylamino-4-keto-hexanoicacid, 1-naphthalenepropanol, alpha.-ethyldecahydro-5-(hydroxymethyl)- (19.97%), 5-O-methyl-d-gluconic acid dimethylamide (19.11%), 5-O-methyl-d-gluconic acid dimethyl-amide (16.16%), least % was observed for 3,6-methano-8h-1,5,7-trioxacyclopenta [IJ] cycloprop [a] azulene-4,8(3H)- (1.35%). The compounds were predicted based on the comparison with NIST database.
TABLE 1A: PROSPECTIVE COMPOUNDS IN ETHANOL EXTRACTS OF A. FERRUGINEA BARK IDENTIFIED BY GC-MS ANALYSIS
|S. no.||RT||Compound name|
|1||18.980||Benzeneethanamine, N,alpha-dimethyl /(Levmetamfetamine)|
|3||21.701||Germacra-1(10),11(13)-dien-12-oic acid, 4,5-alpha-epoxy-6-beta-hydro (Parthenolide)|
|4||23.517||2-Hexanone, 6-Hydroxy- / (6-Hydroxy Hexan-2-one)|
|8||29.239||Androstan-17-one, 3-ethyl-3-hydroxy-, (5 alpha)|
TABLE 1B: PROSPECTIVE COMPOUNDS IN ETHANOL EXTRACTS OF A. FERRUGINEA LEAVES IDENTIFIED BY GC-MS ANALYSIS
|S. no.||RT||Compound name|
|1||17.814||Benzamide, N-[2-[4-[[5-(3,3-dimethyloxiranyl)-4-hydroxy-3-methyl-2-pentenyl]oxy]phenyl]ethyl]- (Severin)|
|3||20.721||5-O-Methyl-D-gluconic acid dimethylamide|
|5||24.387||6,10-Dodecadien-1-yn-3-ol, 3,7,11-trimethyl- /(Dehydronerolidol)
2,6,10-Dodecatrien-1-ol, 3,7,11-trimethyl-, (Z,E)- /(2Z,6E-Farnesol)
|7||28.264||Kauren-18-ol, acetate, (4 beta.)-|
FIG. 4A: GC-MS CHROMATOGRAM OF ETHANOL EXTRACT OF A. FERRUGINEA BARK
FIG. 4B: GC-MS CHROMATOGRAM OF ETHANOL EXTRACT OF A. FERRUGINEA LEAVES
Molecular Docking Analysis: Molecular docking was performed for 19 compounds identified from GC-MS results against CviR protein and higher binding affinity found in severin (-8.862 kcal/ mol) and (2Z,6E)-Farnesol (-6.141 kcal /mol) when compared to the native ligad C6-HSL (-7.052). Comparing to the key amino acids of CviR Asp 97, Trp 84, Ser 155, Severin forms 2 H-bonds (with Asp 97 and Ser 155) and all other compounds have at least 1 H bond except 6-hydroxyhexan-2-one. Fig. 5 and 5A shows the interaction map of the compounds from A. ferruginea. Both Parthenolide and Dehydronerolidol showed H-bond interactions with Asp 97. Docking results of probable compounds from A. ferruginea extracts based on GC-MS results were shown in Table 2. Conventional treatment of alluring ailments depends on natural compounds that aim to kill or restrain bacterial development 19. Recently, plant based natural therapy, as an alternative substitute, gaining global importance because of increased traditional use and cultural acceptability of medicinal plants. Though, plants are continuously subjected to bacterial diseases, they have evolved with sophisticated chemical processes to counter pathogens and they are one of the main sources of chemicals currently being used in diverse sectors, from cosmetic, pharmaceutical, textiles to food biotechnology.
TABLE 2: MOLECULAR INTERACTIONS BETWEEN A. FERRUGINEA COMPOUNDS AND CVIR
FIG. 5: THE 2D INTERACTION DIAGRAMS OF QSIS AGAINST CVIR. THE H-BONDS WERE SHOWN WITH PURPLE ARROWS AND Π-Π WAS SHOWN BY GREEN LINES. INTERACTION MAP OF C6HSL IS (A), (B) FOR INTERACTION MAP OF SEVERIN, (C) FOR INTERACTION MAP OF (2Z, 6E)-FARNESOL, (D) FOR INTERACTION MAP OF DEHYDRONEROLIDOL, (E) FOR INTERACTION MAP OF PARTHENOLIDE, (F) FOR INTERACTION MAP OF LEVMETAFETAMINE AND (G) FOR INERACTION MAP OF 6-HYDROXY-HEXANE-2-ONE AGAINST CVIR.
FIG. 5A: THE 2D INTERACTION DIAGRAMS OF SEVERINWITH CVIR. THE H-BONDS WERE SHOWN WITH PURPLE ARROWS AND Π-Π WAS SHOWN BY GREEN LINES
In comparison with synthetic drugs, natural medications are cost-effective and being embraced by most developing countries 20, 21. In this study, 10 extracts from A. ferruginea leaves and bark were tested for their anti-QS study. Ethanolic extract of both leaf and bark parts of the plant inhibited violacein production and hence were chosen for further studies. Since quorum sensing regulates gene expression, including virulence determinants through a sensory cue and responding system that is based on bacterial cell density, it serves as an attractive target in novel anti-infective development and an enticing approach to countering bacterial infections. As it does not impose any selection pressure, it is unlikely to develop multidrug resistant pathogens 20. In infectious diseases, biofilms perform an important role and most restorative contaminations are because of bacterial biofilms. Nosocomial diseases (60–70%) are likewise due to the arrangement of a biofilm 22. Adverse biofilms are reason for a number of issues ranging from water, food, defilement, bio-consumption to medical diseases 23.
The antimicrobial susceptibility demonstrated by a microorganism/ species to at least one antimicrobial drug in three or more groups of antimicrobials is known as multiple drug resistance (MDR) or multiresistance 24. Since, the development of biofilm results in an increased resistance to multiple drugs, producing and spreading more infectious diseases, there is an emergency need to discover innovative anti-infectives that could control biofilm arrangement and its advancement 25. Quorum sensing enables bacteria to control gene expression which would include the creation of multiple virulence attributes, biofilm formation and swarming motility via cell-to-cell communication. It is based on the response to shifts in population density through chemical signalling molecules called auto-inducers (AIs). It is evidenced that QS accelerates the potency of pathogens in both animal and human models 25, 26.
Cumulative evidence from last two decades, the preventive properties of natural plant products in biofilm formation was confirmed 27. At the highest concentration, both the extracts showed higher inhibition percentage of biofilm. Whereas, at the concentration of 300 and 500 μg/mL the inhibition percentage of leaves was higher when compared to that of bark Fig. 1. Co-culture of medicinal herb extracts (the root bark of Cortex dictamni, Artemisiaeargyi folium and the root of Solanum melongena) considerably reduced the violacein and biofilm production without affecting the growth 28. All the tested concentrations showed significant biofilm inhibition in a dose dependent manner. This is comparable with the previous studies on leaf extracts of selected gardening trees 29. Catechin isolated from Combretum albiflorum reduced biofilm formation in concentration dependent manner 30. From the growth curve analysis of A. ferruginea ethanolic extracts, we found that the growth was unaffected Fig. 2 at all tested concentrations (100- 500 μg/mL). Maximum inhibition of violacein was observed in A. ferruginea leaves (62.84%) and bark (49.81%) at the concentration of 500 μg/mL Fig. 3. Concentration dependent reduction in this study is comparable with previous studies 31, 32, 33, 34.
Major flavonoids from Psidiumguajava like quercetin and quercetin-3-O-glucoside, at 50 and 100μg/mL and ethyl acetate fraction (EAF) of Syzygiumcumini L. and Pimentadioica L at 0.75-1.0 mg/mL concentration showed a significant reduction in violacein production and biofilm formation 31, 32. 95% reduction in violacein production was observed, at 2 μg/Ml, quercetin at 80 μg/mL concentration and malvidin from Syzyium cumini also showed significant anti-QS effects 34. Traditionally, Acacia ferruginea is used to treat many diseases including haemorrhage, irritable bowel syndrome and leprosy 16. Due to its strong antioxidant activity, it is used to treat diseases caused by oxidative and also useful in health supplement production17, 35. Ethanol extracts of leaves of Cassia alata, Mangifera indica and plant parts of Centilla asiatica, inhibited QS regulated phenotypes and showed significant reduction in swarming 36, 37. The extracts of C. sinensis, E. cardamomum, L. nobilis, A. cepa, and C. sativum showed violacein inhibitory actions and a pronounced quorum quenching effect 38.
From GC-MS results it is observed that A. ferruginea possess many active compounds. (2Z, 6E)-Farnesol, appears to have predominant biofilm disruption 39, 40 Parthenolide, as a natural sesquiterpene lactone with anti-inflammation and anticancer activities also had an impact of disturbing pre-established biofilm 41, 42 and biofilm formation was decreased by 56% at 1 mM by pure Parthenolide 43. Nerolidol, inhibited violacein production by ≥50% 44.
Essential oil of Cinnamomum camphora, which contains nerolidol as one of the active components also had a significant inhibitory effect on violacein production and Curcuma longa and vanilla extracts shows significant activity 45-47. The docking score for severin is -8.862 which is higher than the natural ligand C6-HSL (-7.052), that is comparable to that earlier docking studies 4. Similar docking results for CviR and potential QS inhibitor binding are mentioned earlier 4.
According the findings from molecular docking, severine should interact better with C. violaceum. System. CviR's natural ligand, C6-HSL, binds Trp-84, with Tyr-84, Asp-97 and Ser-155 to create hydrogen bonds. Severine binds to the Ser-155 and Asp-97 through polar interactions. As mentioned here, C6-HSL has been documented to bind to CviR through hydrogen bonds and polar interactions (Asp-97, Trp-84, Ser-155) and via hydrophobic contacts (with Trp-111, Phe-126 and Tyr-80) 4. Severine shows unique interactions with Asp-97 and Ser-155, under the same conditions. The compounds from A. ferruginea can therefore serve as a great promising contribute for the advancement of a novel drug, as it inhibits communication between cells. .
CONCLUSION: It is evident that increasing threat by MDR pathogens must be addressed with higher priority and QS inhibition seems to be one of the most promising strategies. The present work established the efficiency of A. ferruginea in inhibiting the bioﬁlm formation and violacein through in-vitro and in-silico studies. Ethanolic extracts of bark and leaves of A. ferruginea, for the first time, have been reported here to possess significant anti-QS activity against C. violaceum. Isolation of active components from the A. ferruginea extract and assessments on inhibition of virulence and biofilms in these organisms is aimed in future studies.
ACKNOWLEDGEMENT: The authors are thankful to the Avinashilingam Institute for providing us all support and infrastructure for carrying out the work. One of the authors thank the Department of Science and Technology for the Women Scientist A (WoS-A) project (SR/WOS-A/CS/25).
CONFLICTS OF INTEREST: Nil
- Aguilar A, Twardowski T and Wohlgemuth R: Bioeconomy for sustainable development. Biotechnology Journal 2019; 14(8): 1800638.
- Jiang K, Xu Y, Yuan B, Yue Y, Zhao M, Luo R, Wu H, Wang L, Zhang Y, Xiao J and Lin F: Effect of Autoinducer-2 Quorum Sensing Inhibitor on Interspecies Quorum Sensing, Frontiers in Microbiology 2022; 13(3).
- Lazar V, Holban AM, Curutiu C and Chifiriuc MC: Modulation of Quorum Sensing and Biofilms in Less Investigated Gram-Negative ESKAPE Pathogens Front. Microbiol 2021; 12: 676510.
- Ravichandran V, Zhong L, Wang H, Yu G, Zhang Y and Li A: Virtual screening and biomolecular interactions of CviR-based quorum sensing inhibitors against Chromobacterium violaceum, Frontiers in Cellular and Infection Microbiology 2018; 8(SEP).
- Subramanian K, Selvaraj H, Balakrishnan K, Sampath Renuga P, Velmurugan S and Aruni W: Anti-Quorum Sensing in Pathogenic Microbes Using Plant-Based Bioactive Phytochemicals, Advances in Materials Science and Engineering 2022;
- Elekhnawy E, Negm WA, El-Aasr M, Kamer AA, Alqarni M, Batiha GES, Obaidullah AJ and Fawzy HM: Histological assessment, anti-quorum sensing, and anti-biofilm activities of Dioonspinulosum extract: in-vitro and in vivo approach, Scientific Reports 2022; 12(1): 1–15.
- Kothari V, Sharma S and Padia D: Recent research advances on Chromobacterium violaceum, Asian Pacific Journal of Tropical Medicine 2017; 10(8): 744–752.
- Santajit S, Sookrung N and Indrawattana N: Quorum Sensing in ESKAPE Bugs: A Target for Combating Antimicrobial Resistance and Bacterial Virulence Biology 2022; 11(10): 1466.
- Chernin LS, Winson MK., Thompson JM, Haran S, Bycroft BW, Chet I, Williams P and Stewart GSAB: Chitinolytic activity in Chromobacterium violaceum: Substrate analysis and regulation by quorum sensing, Journal of Bacteriology 1998; 180(17): 4435–4441.
- Poli JP, Guinoiseau E, de Rocca Serra D, Sutour S, Paoli M, Tomi F, Quilichini Y, Berti L and Lorenzi V: Anti-Quorum Sensing Activity of 12 Essential Oils on Chromobacterium violaceum and Specific Action of cis-cis-p-Menthenolide from Corsican Menthasuaveolens ssp. Insularis, Molecules 2018; 23(9): 2125.
- Durán N, Justo, GZ, Durán M, Brocchi M, Cord L, Tasic L, Castro GR and Nakazato G: Advances in Chromobacterium violaceum and properties of violacein-Its main secondary metabolite: A review, Biotechnology Advances Elsevier Inc 2016; 34(5): 1030–1045.
- Vetrivel A, Ramasamy M, Vetrivel P, Natchimuthu S, Arunachalam S, Kim GS and Murugesan R: Pseudomonas aeruginosa Biofilm Formation and Its Control, Biologics 2021; 1(3): 312–336.
- Abudoleh SM and Mahasneh AM: Anti-Quorum Sensing Activity of Substances Isolated from Wild Berry Associated Bacteria, Avicenna J Med Biotechnol 2017; 9(1): 23-30.
- Bukhari IA, Khan RA, Gilani AH, Ahmed S and Saeed SA: Analgesic, anti-inflammatory and anti-platelet activities of the methanolic extract of Acacia modesta leaves, Inflammopharmacology 2010; 18(4): 187–196. https://doi.org/10.1007/s10787-010-0038-4
- Jeevitha M, Ravi PV, Subramaniyam V Pichumani M and Sripathi KS: Exploring the phyto- and physicochemical evaluation, fluorescence characteristics and antioxidant activities of Acacia ferruginea Dc: an endangered medicinal plant, Futur J Pharm Sci 2021; (7): 228.
- Sakthivel KM and Guruvayoorappan C: Acacia ferruginea inhibits inflammation by regulating inflammatory iNOS and COX-2. Journal of Immunotoxicology 2016; 13(1): 127–135.
- Sowndhararajan K, Hong S, Jhoo JW, Kim S and Chin NL: Effect of acetone extract from stem bark of Acacia species ( dealbata, A. ferruginea and A. leucophloea) on antioxidant enzymes status in hydrogen peroxide-induced HepG2 cells. Saudi Journal of Biological Sciences 2015; 22(6): 685–691.
- Bouyahya A, Dakka, N, Et-Touys A, Abrini J and Bakri Y: Medicinal plant products targeting quorum sensing for combating bacterial infections, Asian Pacific Journal of Tropical Medicine 2017; 10(8): 729–743.
- Koh CL, Sam CK, Yin WF, Tan LY, Krishnan T, Chong YM and Chan KG: Plant-Derived Natural Products as Sources of Anti-Quorum Sensing Compounds. Sensors 2013; 13(5): 6217-6228.
- Zahra W, Rai SN, Birla H, Singh SS, Dilnashin H, Rathore AS and Singh SP: The global economic impact of neurodegenerative diseases: Opportunities and challenges. Bioeconomy for Sustainable Development 2020; 333-45.
- López Y and Soto SM: The preventing usefulness biofilm microalgae infections compounds for preventing biofilm infections. Antibiotics 2020; 9(1): 4 MDPI AG.
- Xu Y, Dhaouadi Y, Stoodley P and Ren D: Sensing the unreachable: challenges and opportunities in biofilm detection, Current Opinion in Biotechnology 2020; 64: 79–84.
- Magiorakos A P, Srinivasan, A, Carey, RB, Carmeli Y, Falagas ME, Giske CG, Harbarth S, Hindler JF, Kahlmeter G, Olsson-Liljequist B, Paterson DL, Rice LB, Stelling J, Struelens MJ, Vatopoulos A, Weber JT and Monnet DL: Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance, Clinical Microbiology and Infection 2012; 18(3): 268–281.
- Camilli A and Bassler BL: Bacterial small-molecule signaling pathways. Science 2006; 311(5764): 1113–1116.
- Castillo-Juárez I, Maeda T, Mandujano-Tinoco EA, Tomás M, Pérez-Eretza B and García-Contreras SJ: Wood TK and García-Contreras R. Role of quorum sensing in bacterial infections, World J of Clinical Cases 2015; 3(7): 575.
- Lu L, Hu W, Tian Z, Yuan D, Yi G, Zhou Y, Cheng Q, Zhu J and Li M: Developing natural products as potential anti-biofilm agents, Chinese Medicine 2019; 14(1): 1-7.
- Wei Q, Bhasme P, Wang Z, Wang L, Wang S, Zeng Y, Wang Y, Ma LZ and Li Y: Chinese medicinal herb extract inhibits PQS-mediated quorum sensing system in Pseudomonas aeruginosa. Journal of Ethnopharmacology 2019; 112272.
- Niu K, Kuk M, Jung H, Chan K and Kim S: Leaf Extracts of Selected Gardening Trees Can Attenuate Quorum Sensing and Pathogenicity of Pseudomonas aeruginosa. Indian Journal of Microbiology 2017; 57(3): 329–338.
- Vandeputte OM, Kiendrebeogo M, Rajaonson S, Diallo B, Mol A, Jaziri M El and Baucher M: Identification of catechin as one of the flavonoids from Combretum albiflorum bark extract that reduces the production of quorum-sensing-controlled virulence factors in Pseudomonas aeruginosa PAQ1, Applied and Environmental Microbiology 2010; 76(1): 243–253.
- Vasavi HS, Arun AB and Rekha PD: Inhibition of quorum sensing in Chromobacterium violaceum by Syzygium cumini and Pimenta dioica L, Asian Pacific Journal of Tropical Biomedicine 2013; 3(12): 954–959.
- Parasuraman P, Devadatha B, Sarma VV, Ranganathan S, Ampasala DR and Siddhardha B: Anti-quorum sensing and antibiofilm activities of Blastobotrysparvus PPR3 against Pseudomonas aeruginosa PAO1. Microbial Pathogenesis 2020; 138: 103811.
- Juan V, Ramírez-ch E, Gutierrez-villagomez JM, García-gonz JP and Molina-torres J: Bioautography and GC-MS based identi fi cation of piperine and trichostachine as the active quorum quenching compounds in black pepper. Heliyon 2020.
- Gopu V, Kothandapani S and Shetty PH: Quorum quenching activity of Syzygiumcumini (L.) Skeels and its anthocyanin malvidin against Klebsiella pneumonia, Microb Pathog 2015; 79: 61-9.
- Thippeswamy S, Abhishek RU, Manjunath K and Mohana DC: Evaluation of antibacterial and antioxidant properties of some traditional medicinal plants from India, International Journal of Green Pharmacy 2015; 9(1): 50–57.
- Zahin M, Hasan S, Aqil F, Khan MSA, Husain FM and Ahmad I: Screening of certain medicinal plants from India for their anti-quorum sensing activity, Indian J ExpBiol 2010; 48: 1219–1224.
- Vasavi HS, Arun AB and Rekha PD: Anti-quorum sensing activity of flavonoid- rich fraction from Centella asiatica against Pseudomonas aeruginosa PAO1. Journal of Microbiology Immunology and Infection 2014; 1–8. https://doi.org/10.1016/j.jmii.2014.03.012
- Al-Haidari RA, Shaaban MI, Ibrahim SRM and Mohamed GA: Anti-quorum sensing activity of some medicinal plants. African Journal of Traditional Complementary and Alternative Medicines 2016; 13(5): 67–71.
- Bandara HMHN, Herpin MJ, Kolacny D, Harb A, Romanovicz D and Smyth HDC: Incorporation of Farnesol Significantly Increases the Efficacy of Liposomal Ciprofloxacin against Pseudomonas aeruginosa Biofilms in-vitro. Molecular Pharmaceutics 2016; 13(8): 2760–2770.
- D’Angelo F, Baldelli V, Halliday N, Pantalone P, Polticelli F, Fiscarelli E, Williams P, Visca P, Leoni L and Rampioni G: Identification of FDA-Approved Drugs as Antivirulence Agents Targeting the pqs Quorum-Sensing System of Pseudomonas aeruginosa, Antimicrobial Agents and Chemotherapy 2018; 62(11).
- Mathema VB, Koh YS, Thakuri BC and Sillanpää M: Parthenolide, a sesquiterpene lactone, expresses multiple anti-cancer and anti-inflammatory activities. Inflammation 2012; 35(2): 560–565.
- Tang H, Hao S, Khan M F, Zhao L, Shi F, Li Y, Guo H, Zou Y, Lv C, Luo J, Zeng Z, Wu Q and Ye G: Epigallocatechin-3-Gallate Ameliorates Acute Lung Damage by Inhibiting Quorum-Sensing-Related Virulence Factors of Pseudomonas aeruginosa, Frontiers in Microbiology 2022; 13.
- Kalia M, Yadav VK, Singh PK, Sharma D, Narvi SS and Agarwal V: Exploring the impact of parthenolide as anti-quorum sensing and anti-biofilm agent against Pseudomonas aeruginosa, Life Sciences 2018; 199.
- Ahmad A, Viljoen AM & Chenia HY: The impact of plant volatiles on bacterial quorum sensing, Letters in Applied Microbiology 2015; 60(1): 8–19.
- Wang W, Li D, Huang X, Yang H, Qiu Z, Zou L, Liang Q, Shi Y, Wu Y, Wu S, Yang C and Li Y: Study on Antibacterial and Quorum-Sensing Inhibition Activities of Cinnamomum camphora Leaf Essential Oil, Molecules 2019; 24(20):3792. Bouyahya A, Chamkhi I, Balahbib A, Rebezov M, Shariati MA, Wilairatana P, Mubarak MS, Benali T and El Omari N: Mechanisms, Anti-Quorum-Sensing Actions, and Clinical Trials of Medicinal Plant Bioactive Compounds against Bacteria: A Comprehensive Review. Molecules 2022; 27(5).
- İnat G, Sırıken B, Başkan C, Erol İ, Yıldırım T and Çiftci A: Quorum sensing systems and related virulence factors in Pseudomonas aeruginosa isolated from chicken meat and ground beef. Scientific Reports 2021; 11(1): 1-9.
- Packiavathy IAS, Priya S, Pandian SK and Ravi AV: Inhibition of biofilm development of uropathogens by curcumin - An anti-quorum sensing agent from Curcuma longa. Food Chemistry 2014; 148: 453–460.
- Choo JH, Rukayadi Y and Hwang JK: Inhibition of bacterial quorum sensing by vanilla extract. Letters in Applied Microbiology 2006; 42(6): 637–641.
- Friesner RA, Murphy RB, Repasky MP, Frye LL, Greenwood JR, Halgren TA, Sanschagrin PC and Mainz DT: Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J Med Chem 2006; 49(21): 6177-96.
How to cite this article:
Jeevitha M, Ravichandran V and Sripathi SK: Molecular docking and biological evaluation of Acacia ferruginea and its active principle, severin, against Chromobacterium violaceum. Int J Pharm Sci & Res 2023; 14(4): 1861-71. doi: 10.13040/IJPSR.0975-8232.14(4).1861-71.
All © 2023 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
M. Jeevitha *, Vinothkannan Ravichandran and Shubashini K. Sripathi
Department of Chemistry, Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore, Tamil Nadu, India.
18 August 2018
28 December 2018
17 January 2019
01 April 2023