scholarly journals A Novel Small Molecule, LCG-N25, Inhibits Oral Streptococcal Biofilm

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoying Lyu ◽  
Chungen Li ◽  
Jin Zhang ◽  
Liang Wang ◽  
Qingsong Jiang ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Drug Resistance ◽  
Dental Caries ◽  
Antimicrobial Agent ◽  
Small Molecule ◽  
Cell Counting ◽  
Tooth Surface ◽  
Extracellular Polysaccharides ◽  
Fluorescent Staining ◽  
Microbial Composition

Dental caries is a chronic oral infectious disease caused by cariogenic biofilm adhered on the tooth surface. Our previous study demonstrated that a repurposed natural compound napabucasin (NAP) showed good antimicrobial activity against oral streptococcal biofilms. The current study designed a novel small molecule, namely LCG-N25, using NAP as a lead compound, and aimed to investigate its potential as an antimicrobial agent in the control of dental caries. LCG-N25 was designed and synthesized with reference to the structure of NAP. The minimal inhibitory concentrations and the minimal bactericidal concentrations of LCG-N25 against Streptococcus mutans, Streptococcus sanguinis, and Streptococcus gordonii were evaluated by microdilution method. The antimicrobial activity of LCG-N25 was further evaluated by crystal violet staining, colony forming units counting, biofilm metabolism assay, dead/live fluorescent staining, and scanning electron microscopy. The effect of LCG-N25 on the extracellular polysaccharides of biofilms was determined by both anthrone-sulfuric acid method and fluorescent staining. The microbial composition of streptococcal biofilms after LCG-N25 treatment was further visualized and quantified by fluorescence in situ hybridization. Besides, the cytotoxicity of LCG-N25 was evaluated by Cell Counting Kit-8 assay, and repeated exposure of S. mutans to LCG-N25 treatment was performed to assess if this novel compound could induce drug resistance of this cariogenic bacterium. We found that LCG-N25 exhibited a good antibacterial activity, low-cytotoxicity, and did not induce drug resistance of cariogenic S. mutans. These findings suggest that LCG-N25 may represent a promising antimicrobial agent that can be used as an adjuvant to the management of dental caries.

scholarly journals Application of Green Synthesized Iron Nanoparticles for Enhanced Antimicrobial Activity of Selected Traditional and Commonly Exploited Drug Amoxicillin Against Streptococcus mutans

2017 ◽  
Vol 14 (3) ◽  
pp. 1135-1141 ◽  
Author(s):  
Gudaniya Kasthuri ◽  
A. Neethi Reddy ◽  
P. Manasa Roopa ◽  
Deveeka. K. Zamare
Keyword(s):  
Antimicrobial Activity ◽  
Drug Resistance ◽  
Dental Caries ◽  
Streptococcus Mutans ◽  
Plant Extract ◽  
Iron Nanoparticles ◽  
Syzygium Aromaticum ◽  
Tea Leaves ◽  
Neem Leaves ◽  
Green Tea Leaves

ABSTRACT: The development of drug resistance in pathogens due to over exploitation of the drugs is urging the need of finding alternative method for controlling the growth of these pathogens. The dental biofilms development leads to the dental caries which when neglected can be serious. The oral biofilm is a complex colonization of different pathogens, whereas Streptococcus mutans paves the path for the formation of these stubborn biofilms by makeing use of dietary sugars and accumulates on tooth surface through exopolysaccharides (EPS). The current life style and eating habits are favoring the plaque development leading in to dental caries. Here we amide to eliminate the dread of development of drug resistance in to the pathogens by mechanical damage and combination of treatment as an alternate option for destruction of Streptococcus mutans. This was accomplished by the application of Iron Nanoparticles (FeNP). It was observed that the antimicrobial activity of natural and synthetic drugs can be enhanced by the synergy of FeNP. The popular natural products like Syzygium aromaticum (Clove) buds, Azadirachta indica (Neem) leaves and Camellia sinensis (Green tea) leaves were tested for their activity against the Streptococcus mutans. The enhanced antimicrobial activity were tested by treating Streptococcus mutans with different combination of treatments like only plant extract, Plant extract with FeNP, plant extract with FeNP and Amoxicillin to obtain a comparative analysis of its effects. The study showed that the activity of antimicrobial agent can be enhanced when added with FeNP. The FeNP were green synthesized from the extracts of Syzygium aromaticum (Clove) buds, Azadirachta indica (Neem) leaves and Camellia sinensis (Green tea) leaves and was characterized by UV,FTIR and SEM studiesand zeta potential studies.

scholarly journals A Novel Small Molecule, ZY354, Inhibits Dental Caries-Associated Oral Biofilms

2019 ◽  
Vol 63 (5) ◽  
Author(s):  
Chenzi Zhang ◽  
Xinyi Kuang ◽  
Yuanzheng Zhou ◽  
Xian Peng ◽  
Qiang Guo ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Dental Caries ◽  
Small Molecule ◽  
Laser Scanning Microscopy ◽  
Oral Streptococci ◽  
Biofilm Inhibition ◽  
Content Type ◽  
Small Molecule Compound ◽  
Low Cytotoxicity ◽  
Multispecies Biofilms

ABSTRACT Biofilm control is a critical approach to the better management of dental caries. Antimicrobial small molecules have shown their potential in the disruption of oral biofilm and control of dental caries. The objectives of this study were to examine the antimicrobial activity and cytotoxicity of a newly designed small-molecule compound, ZY354. ZY354 was synthesized, and its cytotoxicity was evaluated in human oral keratinocytes (HOK), human gingival epithelial cells (HGE), and macrophages (RAW) by CCK-8 assays. Minimal inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs), minimum biofilm inhibition concentrations (MBICs), and minimum biofilm reduction concentrations (MBRCs) of ZY354 against common oral streptococci (i.e., Streptococcus mutans, Streptococcus gordonii, and Streptococcus sanguinis) were determined by microdilution method. The exopolysaccharide (EPS)/bacterium ratio and the dead/live bacterium ratio in the ZY354-treated multispecies biofilms were determined by confocal laser scanning microscopy, and the microbial composition was visualized and quantified by fluorescent in situ hybridization and quantitative PCR (qPCR). The demineralizing activity of ZY354-treated biofilms was evaluated by transverse microradiography. The results showed that ZY354 exhibited low cytotoxicity in HOK, HGE, and RAW cells and exhibited potent antimicrobial activity against common oral streptococci. The EPS and the abundance of S. mutans were significantly reduced after ZY354 treatment, along with an increased dead/live microbial ratio in multispecies biofilms compared to the level with the nontreated control. The ZY354-treated multispecies biofilms exhibited reduced demineralizing activity at the biofilm/enamel interface. In conclusion, the small-molecule compound ZY354 exhibits low cytotoxicity and remarkable antimicrobial activity against oral streptococci, and it may have a great potential in anticaries clinical applications.

scholarly journals The Effect of Essential Oils and Bioactive Fractions onStreptococcus mutansandCandida albicansBiofilms: A Confocal Analysis

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Irlan Almeida Freires ◽  
Bruno Bueno-Silva ◽  
Lívia Câmara de Carvalho Galvão ◽  
Marta Cristina Teixeira Duarte ◽  
Adilson Sartoratto ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Dental Caries ◽  
Essential Oils ◽  
Translational Research ◽  
Streptococcus Mutans ◽  
Statistical Difference ◽  
Oral Candidiasis ◽  
Extracellular Polysaccharides ◽  
Oral Biofilms ◽  
Strong Antimicrobial Activity

The essential oils (EO) and bioactive fractions (BF) fromAloysia gratissima, Baccharis dracunculifolia, Coriandrum sativum, Cyperus articulatus,andLippia sidoideswere proven to have strong antimicrobial activity on planktonic microorganisms; however, little is known about their effects on the morphology or viability of oral biofilms. Previously, we determined the EO/fractions with the best antimicrobial activity againstStreptococcus mutansandCandidaspp. In this report, we used a confocal analysis to investigate the effect of these EO and BF on the morphology ofS. mutansbiofilms (thickness, biovolume, and architecture) and on the metabolic viability ofC. albicansbiofilms. The analysis of intact treatedS. mutansbiofilms showed no statistical difference for thickness in all groups compared to the control. However, a significant reduction in the biovolume of extracellular polysaccharides and bacteria was observed forA. gratissimaandL. sidoidesgroups, indicating that these BF disrupt biofilm integrity and may have created porosity in the biofilm. This phenomenon could potentially result in a weakened structure and affect biofilm dynamics. Finally,C. sativumEO drastically affectedC. albicansviability when compared to the control. These results highlight the promising antimicrobial activity of these plant species and support future translational research on the treatment of dental caries and oral candidiasis.

scholarly journals Repurposing Napabucasin as an Antimicrobial Agent against Oral Streptococcal Biofilms

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Xinyi Kuang ◽  
Tao Yang ◽  
Chenzi Zhang ◽  
Xian Peng ◽  
Yuan Ju ◽  
...  
Keyword(s):  
Dental Caries ◽  
Laser Scanning ◽  
Antibacterial Activities ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Oral Streptococci ◽  
Oral Keratinocytes ◽  
Microbial Composition ◽  
Biofilm Inhibition ◽  
Multispecies Biofilms

Objectives. Disruption of microbial biofilms is an effective way to control dental caries. Drug resistance and side effects of the existing antimicrobials necessitate the development of novel antibacterial agents. The current study was aimed at investigating the antibacterial activities of the repurposed natural compound napabucasin against oral streptococci. Methods. The minimum inhibitory concentration, minimum bactericidal concentration, minimum biofilm inhibition concentration, and minimum biofilm reduction concentration of Streptococcus mutans, Streptococcus gordonii, and Streptococcus sanguinis were examined by a microdilution method. Cytotoxicity of napabucasin against human oral keratinocytes, human gingival epithelia, and macrophage RAW264.7 was evaluated by CCK8 assays. The dead/live bacterium and exopolysaccharide in the napabucasin-treated multispecies biofilms were evaluated by confocal laser scanning microscopy. Microbial composition within the napabucasin-treated biofilms was further visualized by fluorescent in situ hybridization and qPCR. And the cariogenicity of napabucasin-treated biofilms was evaluated by transverse microradiography. Results. Napabucasin exhibited good antimicrobial activity against oral streptococcal planktonic cultures and biofilms but with lessened cytotoxicity as compared to chlorhexidine. Napabucasin reduced the cariogenic S. mutans and increased the proportion of the commensal S. gordonii in the multispecies biofilms. More importantly, napabucasin significantly reduced the demineralization capability of biofilms on tooth enamels. Conclusion. Napabucasin shows lessened cytotoxicity and comparable antimicrobial effects to chlorhexidine. Repurposing napabucasin may represent a promising adjuvant for the management of dental caries.

scholarly journals Drug-Like Small Molecule HSP27 Functional Inhibitor Sensitizes Lung Cancer Cells to Gefitinib or Cisplatin by Inducing Altered Cross-Linked Hsp27 Dimers

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 630
Author(s):  
Hawon Yoo ◽  
Seul-Ki Choi ◽  
Jaeok Lee ◽  
So Hyeon Park ◽  
You Na Park ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Cell Lines ◽  
Small Molecule ◽  
Anticancer Agents ◽  
Tumor Growth Inhibition ◽  
Dependent Manner ◽  
Hsp27 Expression ◽  
Cancer Aggressiveness

Relationships between heat shock protein 27 (HSP27) and cancer aggressiveness, metastasis, drug resistance, and poor patient outcomes in various cancer types including non-small cell lung cancer (NSCLC) were reported, and inhibition of HSP27 expression is suggested to be a possible strategy for cancer therapy. Unlike HSP90 or HSP70, HSP27 does not have an ATP-binding pocket, and no effective HSP27 inhibitors have been identified. Previously, NSCLC cancer cells were sensitized to radiation and chemotherapy when co-treated with small molecule HSP27 functional inhibitors such as zerumbone (ZER), SW15, and J2 that can induce abnormal cross-linked HSP27 dimer. In this study, cancer inhibition effects of NA49, a chromenone compound with better solubility, longer circulation time, and less toxicity than J2, were examined in combination with anticancer drugs such as cisplatin and gefitinib in NSCLC cell lines. When the cytotoxic drug cisplatin was treated in combination with NA49 in epidermal growth factor receptors (EGFRs) WT cell lines, sensitization was induced in an HSP27 expression-dependent manner. With gefitinib treatment, NA49 showed increased combination effects in both EGFR WT and Mut cell lines, also with HSP27 expression-dependent patterns. Moreover, NA49 induced sensitization in EGFR Mut cells with a secondary mutation of T790M when combined with gefitinib. Augmented tumor growth inhibition was shown with the combination of cisplatin or gefitinib and NA49 in nude mouse xenograft models. These results suggest the combination of HSP27 inhibitor NA49 and anticancer agents as a candidate for overcoming HSP27-mediated drug resistance in NSCLC patients.

Small-molecule degraders of cyclin-dependent kinase protein: a review

2021 ◽  
Author(s):  
Bin Yu ◽  
Zekun Du ◽  
Yuming Zhang ◽  
Zhiyu Li ◽  
Jinlei Bian
Keyword(s):  
Cell Cycle ◽  
Drug Resistance ◽  
Protein Degradation ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Structural Characteristics ◽  
Protein A ◽  
Cyclin Dependent Kinase ◽  
Chemical Tools ◽  
Potential Therapeutics

Proteolysis-targeting chimeras are a new modality of chemical tools and potential therapeutics involving the induction of protein degradation. Cyclin-dependent kinase (CDK) protein, which is involved in cycles and transcription cycles, participates in regulation of the cell cycle, transcription and splicing. Proteolysis-targeting chimeras targeting CDKs show several advantages over traditional CDK small-molecule inhibitors in potency, selectivity and drug resistance. In addition, the discovery of molecule glues promotes the development of CDK degraders. Herein, the authors describe the existing CDK degraders and focus on the discussion of the structural characteristics and design of these degraders.

scholarly journals The Designer Antimicrobial Peptide A-hBD-2 Facilitates Skin Wound Healing by Stimulating Keratinocyte Migration and Proliferation

2018 ◽  
Vol 51 (2) ◽  
pp. 647-663 ◽  
Author(s):  
Bobin Mi ◽  
Jing Liu ◽  
Yi Liu ◽  
Liangcong Hu ◽  
Yukun Liu ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Wound Healing ◽  
Antimicrobial Peptide ◽  
Structural Stability ◽  
Cell Counting ◽  
Sprague Dawley ◽  
Skin Wound Healing ◽  
High Sodium

Background/Aims: Antimicrobial peptides are effective promoters of wound healing but are susceptible to degradation. In this study, we replaced the GIGDP unit on the N-terminal of the endogenous human antimicrobial peptide hBD-2 with APKAM to produce A-hBD-2 and analyzed the effect on wound healing both in vitro and in vivo. Methods: The effects of A-hBD-2 and hBD-2 on cytotoxicity and proliferation in keratinocytes were assessed by Cell Counting Kit-8 assay. The structural stability and antimicrobial activity of hBD-2 and A-hBD-2 were evaluated against Staphylococcus aureus. RNA and proteins levels were evaluated by real-time PCR and western blotting, respectively. Cell migration was evaluated using a transwell assay. Cell cycle analysis was performed by flow cytometry. Wound healing was assessed in Sprague-Dawley rats. Epidermal thickness was evaluated by hematoxylin and eosin staining. Results: We found that hBD-2 exhibited cytotoxicity at high concentrations and decreased the structural stability in the presence of high sodium chloride concentrations. A-hBD-2 exhibited increased structural stability and antimicrobial activity, and had lower cytotoxicity in keratinocytes. A-hBD-2 increased the migration and proliferation of keratinocytes via phosphorylation of EGFR and STAT3 and suppressed terminal differentiation of keratinocytes. We also found that A-hBD-2 elicited mobilization of intracellular Ca2+ and stimulated keratinocytes to produce pro- and anti-inflammatory cytokines and chemokines via phospholipase C activation. Furthermore, A-hBD-2 promoted wound healing in vivo. Conclusion: Our data suggest that A-hBD-2 may be a promising candidate therapy for wound healing.

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