Investigation of Phloroglucinol Succinic Acid Dendrimer as Antimicrobial Agent Against Staphylococcus Aureus, Escherichia Coli and Candida Albicans (original) (raw)
Related papers
2007
Nearly 3 decades ago, a dendritic structure was stepwise synthesized for the first time as a new type of molecules with promising applications. During years a huge effort has been devoted to implement the synthetic skills concerning the synthesis of these molecules and especially, new methods for purification and characterization of these compounds that are in the nanoscale range. The chemical manipulation of the surface and inner core of dendrimers were strategically used to allow a tailor-made control of physical-chemical properties and to discover new applications in material science and biomedicine. Although several examples have been reported in the literature describing applications of functionalized dendrimers and acclaiming a key role of these molecules, very scarce examples are actually close to the market. This review summarizes the state of the art of dendrimers and dendritic polymers as anti-infective agents, with a special focus on the strategies to block receptors used by pathogens for attachment, cell entry and dissemination. These nanometre size molecules are very attractive compounds as new drugs easily to be manipulated to improve their activity and scope. This is already a very active area of research, where we are involved, with interesting potential as demonstrated by the Phase I clinical trial of a functionalized dendrimer with real possibilities to reach the market soon. The success of this compound should provoke an enormous stimulus to scientists working in this area as well as in the industrial companies for investment in this topic.
Molecular Pharmaceutics, 2019
52 pH-responsive drug delivery systems are yielding opportunities to directly deliver antibiotics to the site of infection. Therefore, this study aimed to develop and evaluate novel pH-54 responsive lipid-dendrimer hybrid nanoparticles (LDH-NPs) for the delivery of vancomycin 55 (VCM) to the site of infection, by intracellular bacterial pathogens. The LDH-NPs were 56 formulated using the emulsification solvent evaporation method and were characterised by 57 various in vitro and molecular dynamic (MD) simulation techniques. LDH-NPs were 58 124.4±2.01 nm in size, with a zeta-potential of-7.15±2.98 mV and drug entrapment efficiency 59 of 82.70±4.09%, which exhibited pH-responsive behaviour by shifting the surface charge from 60 negative at physiological pH to positive in acidic pHs, with a size increase from 124.4±2.01 to 61 173.9±13.38 nm, and 252.7±3.98 nm at pHs of 7.4, 6.0 and 4.5, respectively. Results indicated 62 that the in vitro drug release of VCM from LDH-NPs occurred faster at pH 6.0 than at pH 7.4. 63 The antibacterial activity of LDH-NPs against methicillin-resistance staphylococcus aureus 64 (MRSA) showed 8-fold lower MICs at pH 6.0 and 7.4, compared to treatment with VCM 65 only. A bacterial cell viability study showed, LDH-NPs had an 84.19% killing of MRSA, 66 compared to VCM (49.26%) at the same MIC, further confirming its efficacy. Cell uptake 67 studies showed that LDH-NPs intracellularly accumulated in HEK 293 cells, confirming 68 significant clearance (p< 0.0001) of intracellular bacteria. MD simulation showed that 69 interaction between the dendrimer and oleylamine was predominantly governed by Van der 70 Waals (VdW) interactions; whereas the interaction between the dendrimer and VCM was 71 governed by both VdW and electrostatic interactions. Therefore, this study concludes that the 72 pH-responsive release of VCM enhanced antibacterial efficacy against MRSA and 73 intracellular delivery of an antibiotic. Thus, LDH-NPs is a promising nanocarrier system for 74 antibiotics with the potential to improve the treatment outcomes of bacterial infections in 75 patients with antibiotic resistant strains.
In vitro antibacterial activity of poly (amidoamine)-G7 dendrimer
BMC Infectious Diseases
Background: Nano-scale dendrimers are synthetic macromolecules that frequently used in medical and health field. Traditional anibiotics are induce bacterial resistence so there is an urgent need for novel antibacterial drug invention. In the present study seventh generation poly (amidoamine) (PAMAM-G7) dendrimer was synthesized and its antibacterial activities were evaluated against representative Gram-negative and Gram-positive bacteria. Methods: PAMAM-G7 was synthesized with divergent growth method. The structural and surface of PAMAM-G7 were investigated by transmission electron microscopy, scanning electron microscope and fourier transform infrared. Pseudomonas. aeruginosa (n = 15), E. coli (n = 15), Acinetobacter baumanni (n = 15), Shigella dysenteriae (n = 15), Klebsiella pneumoniae (n = 10), Proteus mirabilis (n = 15), Staphylococcus aureus (n = 15) and Bacillus subtilis (n = 10) have been used for antibacterial activity assay. Additionally, representative standard strains for each bacterium were included. Minimum Inhibitory Concentration (MIC) was determined using microdilution method. Subsequently, Minimum Bactericidal Concentration (MBC) was determined by sub-culturing each of the no growth wells onto Mueller Hinton agar medium. The cytotoxicity of PAMAM-G7 dendrimer were evaluated in HCT116 and NIH 3 T3 cells by MTT assay. Results: The average size of each particle was approximately 20 nm. PAMAM-G7 was potentially to inhibit both Gram positive and gram negative growth. The MIC50 and MIC90 values were determined to be 2-4 μg/ml and 4-8 μg/ml, respectively. The MBC50 and MBC90 values were found to be 64-256 μg/ml and 128-256 μg/ml, respectively. The cytotoxity effect of dendrimer on HCT116 and NIH 3 T3 cells is dependent upon exposure time to and concentration of dendrimers. The most reduction (44.63 and 43%) in cell viability for HCT116 and NIH 3 T3 cells was observed at the highest concentration, 0.85 μM after 72 h treatmentm, respectively. Conclusions: This study we conclude that PAMAM-G7 dendrimer could be a potential candidate as a novel antibacterial agent.
Journal of Nanomaterials
Dendrimers are potent synergists, carriers, and delivery molecules for natural biological products and pharmaceuticals. Staphylococcus aureus (S. aureus) infection is causing serious diseases in humans and animals. Given the recorded antibacterial and antiviral activity of terminal-charged PAMAM dendrimers, the relation between dendrimer charge type and generation is to be established against S. aureus. Three types of polyanionic dendrimers comprising terminal groups sodium carboxylate (generations 1.5, 2.5, 3.5, and 4.5), hydroxyl (generations 2, 3, 4, and 5), and succinamic acid (generations 2, 3, 4, and 5) and polycationic dendrimers containing primary amine (generations 2, 3, 4, and 5) were in antibacterial assays to determine their zone of inhibition and antibacterial activity. Cationic dendrimers were more potent than anionic dendrimers. The largest inhibition was shown by G(5)-128NH2 followed by G(4)-64NH2 primary amine dendrimers. Carboxylate, hydroxyl, and succinamic acid d...
Surface modification of poly(amidoamine) (PAMAM) dendrimer as antimicrobial agents
Tetrahedron Letters, 2012
Poly(amidoamine) (PAMAM) (G3) dendrimer was modified into quaternary ammonium salts using tertiary amines with different chain lengths: dimethyldodecyl amine, dimethylhexyl amine, and dimethylbutyl amine using an efficient synthetic route. The antimicrobial activity of these dendrimer ammonium salts against Staphylococcus and E-coli bacteria was examined using the disc diffusion method. It was found that quaternary ammonium salt prepared with the dimethyldodecyl amine exhibits antimicrobial efficacy against Staphalococus and E.coli bacteria.
Pyrazole-Based Water-Soluble Dendrimer Nanoparticles as a Potential New Agent against Staphylococci
Biomedicines
Although the antimicrobial potency of the pyrazole nucleus is widely reported, the antimicrobial effects of the 2-(4-bromo-3,5-diphenyl-pyrazol-1-yl)-ethanol (BBB4), found to be active against several other conditions, have never been investigated. Considering the worldwide need for new antimicrobial agents, we thought it noteworthy to assess the minimum inhibitory concentration (MICs) of BBB4 but, due to its scarce water-solubility, unequivocal determinations were tricky. To obtain more reliable MICs and to obtain a substance also potentially applicable in vivo, we recently prepared water-soluble, BBB4-loaded dendrimer nanoparticles (BBB4-G4K NPs), which proved to have physicochemical properties suitable for clinical application. Here, with the aim of developing a new antibacterial agent based on BBB4, the BBB4-G4K NPs were tested on several strains of different species of the Staphylococcus genus. Very low MICs (1.5–3.0 µM), 15.5–124.3-fold lower than those of the free BBB4, were ...
Molecules (Basel, Switzerland), 2017
We report a versatile divergent methodology to construct dendrimers from a tetrafunctional core, utilizing the robust copper(I) catalyzed alkyne-azide cycloaddition (CuAAC, "click") reaction for both dendrimer synthesis and post-synthesis functionalization. Dendrimers of generations 1-3 with 8-32 protected or free OH and acetylene surface groups, were synthesized using building blocks that included acetylene- or azide-terminated molecules with carboxylic acid or diol end groups, respectively. The acetylene surface groups were subsequently used to covalently link cationic amino groups. A preliminary evaluation indicated that the generation one dendrimer with terminal NH₃⁺ groups was the most effective bactericide, and it was more potent than several previously studied dendrimers. Our results suggest that size, functional end groups and hydrophilicity are important parameters to consider in designing efficient antimicrobial dendrimers.
Function Oriented Molecular Design: Dendrimers as Novel Antimicrobials
Molecules, 2017
In recent years innovative nanostructures are attracting increasing interest and, among them, dendrimers have shown several fields of application. Dendrimers can be designed and modified in plentiful ways giving rise to hundreds of different molecules with specific characteristics and functionalities. Biomedicine is probably the field where these molecules find extraordinary applicability, and this is probably due to their multi-valency and to the fact that several other chemicals can be coupled to them to obtain desired compounds. In this review we will describe the different production strategies and the tools and technologies for the study of their characteristics. Finally, we provide a panoramic overview of their applications to meet biomedical needs, especially their use as novel antimicrobials.
Dendrimers: Potential Tool for Enhancement of Antifungal Activity
sphinxsai.com
Nystatin and Terbinafine are antifungal drugs with well-known antifungal properties. In the present study we investigated the potential of PAMAM and PPI dendrimers of different generations as tool for enhancement of antifungal activity of selected two antifungal drugs. Microbilogical study showed that PAMAM and PPI dendrimers could enhance the antifungal activities of Nystatin and Terbinafine against Candida albicans, Aspergillus niger and Sachromyces cerevasae. Results showed increase in the antifungal activity of Nystatin and Terbinafine in dendrimer solution compared to pure Nystatin and Terbinafine dissolved in DMSO (dimethylsulfoxide). The antifungal activity studies indicated that PAMAM and PPI dendrimers as potential tool for enhancement of antifungal activity of Nysatin and Terbinafine.
On the Antimicrobial Activity of Various Peptide-Based Dendrimers of Similar Architecture
Molecules, 2015
Antimicrobial drug resistance is a major human health threat. Among the many attempts to tackle this problem, the synthesis of antimicrobial compounds that mimic natural antimicrobial peptides appears as a promising approach. Peptide-based dendrimers can be designed to have higher potency than natural antimicrobial peptides and at the same time they can evade the bacterial defense system. Novel dendrimers with similar chemical structure but varying potency in terms of minimum inhibitory concentration were designed. The dependency between dendrimer structure and antibacterial activity as well as their capacity to attack model cell membranes was studied. The data suggests that supramolecular structure in terms of charge distribution and amphiphilicity, rather than net charge, is the main driver for disruption of cellular membranes and this correlates well with dendrimer hemolytic activity.