-
Sao Paulo Medical Journal = Revista... 2022Maintenance of oral microbiota balance is the simplest way to prevent infectious oral diseases, through controlling dental biofilm. Combined use of mouthwash and...
BACKGROUND
Maintenance of oral microbiota balance is the simplest way to prevent infectious oral diseases, through controlling dental biofilm. Combined use of mouthwash and mechanical removal has been shown to be a very effective way for this.
OBJECTIVES
To identify clinical studies comparing the antimicrobial effect and possible adverse effects and/or side effects of chlorhexidine-based mouthwashes with those of mouthwashes containing chlorine dioxide and/or polyhexanide, for controlling oral microbiota.
DESIGN AND SETTING
Systematic review designed by the stomatology sector of postgraduation in applied dental sciences of Bauru Dentistry School, University of São Paulo, Brazil.
METHODS
A systematic review was conducted using online databases (PubMed, Embase, Web of Science and Science Direct) up to April 8, 2020. The search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
The studies included comprised eight articles published between 2001 and 2017. A total of 295 young adults, adults and elderly people were evaluated (males 44.75% and females 55.25%). Three articles compared polyhexanide with chlorhexidine and five articles compared chlorine dioxide with chlorhexidine. No studies comparing all three mouthwashes were found. The concentrations of the study solutions were quite varied, and all rinses had an antimicrobial effect. In four studies, it was stated that no side effects or adverse effects had been found. Three studies did not address these results and only one study addressed side effects and/or adverse effects.
CONCLUSION
Mouthwashes containing chlorine dioxide and polyhexanide are viable alternatives to chlorhexidine, since they reduce oral biofilm and have little or no reported side or adverse effects.
Topics: Aged; Biguanides; Chlorhexidine; Chlorine Compounds; Female; Humans; Male; Oxides; Young Adult
PubMed: 34932779
DOI: 10.1590/1516-3180.2020.0776.R1.18052021 -
American Journal of Infection Control Jul 2022The purpose of this study was to evaluate the virucidal activity of a new olanexidine-containing formulation for hand hygiene (olanexidine gluconate hand rub; OLG-HR)...
BACKGROUND
The purpose of this study was to evaluate the virucidal activity of a new olanexidine-containing formulation for hand hygiene (olanexidine gluconate hand rub; OLG-HR) against non-enveloped viruses and to understand its mechanism of action.
METHODS
The virucidal activities of OLG-HR against two strains of caliciviruses and three adenovirus serotypes were evaluated through suspension tests. Also, virus-like particles were used to predict the effect of olanexidine gluconate on virus particle structure.
RESULTS
The results of suspension tests under conditions with and without interfering substances (1.5% BSA) indicated that OLG-HR had a broad-spectrum effect against non-enveloped viruses, and the virucidal effect was unaffected by organic contaminants. Furthermore, olanexidine inhibited the binding ability of virus-like particles to the binding receptor of human norovirus and increased the aggregation of virus-like particles in a dose-dependent manner. Transmission electron microscopy showed that the morphology of the virus-like particles was affected by exposure to olanexidine, indicating that the protein-denaturing effect of olanexidine gluconate caused the loss of receptor-binding capability of the viral capsid protein.
CONCLUSIONS
This study suggests that olanexidine gluconate is a potential biological and environmental disinfectant against norovirus and adenovirus.
Topics: Anti-Infective Agents, Local; Biguanides; Disinfectants; Disinfection; Glucuronates; Humans; Norovirus
PubMed: 34864086
DOI: 10.1016/j.ajic.2021.11.020 -
Cell Metabolism Dec 2018There is increasing interest in therapeutically exploiting metabolic differences between normal and cancer cells. We show that kinase inhibitors (KIs) and biguanides...
There is increasing interest in therapeutically exploiting metabolic differences between normal and cancer cells. We show that kinase inhibitors (KIs) and biguanides synergistically and selectively target a variety of cancer cells. Synthesis of non-essential amino acids (NEAAs) aspartate, asparagine, and serine, as well as glutamine metabolism, are major determinants of the efficacy of KI/biguanide combinations. The mTORC1/4E-BP axis regulates aspartate, asparagine, and serine synthesis by modulating mRNA translation, while ablation of 4E-BP1/2 substantially decreases sensitivity of breast cancer and melanoma cells to KI/biguanide combinations. Efficacy of the KI/biguanide combinations is also determined by HIF-1α-dependent perturbations in glutamine metabolism, which were observed in VHL-deficient renal cancer cells. This suggests that cancer cells display metabolic plasticity by engaging non-redundant adaptive mechanisms, which allows them to survive therapeutic insults that target cancer metabolism.
Topics: Adaptor Proteins, Signal Transducing; Amino Acids; Animals; Antineoplastic Combined Chemotherapy Protocols; Biguanides; Cell Cycle Proteins; Drug Resistance, Neoplasm; Eukaryotic Initiation Factors; Gene Expression Regulation, Neoplastic; HCT116 Cells; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; K562 Cells; Mechanistic Target of Rapamycin Complex 1; Mice; Mice, Nude; Neoplasms; Phosphoproteins; Protein Kinase Inhibitors; RNA, Messenger; Signal Transduction; Xenograft Model Antitumor Assays
PubMed: 30244971
DOI: 10.1016/j.cmet.2018.09.001 -
Biochemistry Sep 2017Metformin is the most commonly prescribed treatment for type II diabetes and related disorders; however, molecular insights into its mode(s) of action have been limited...
Metformin is the most commonly prescribed treatment for type II diabetes and related disorders; however, molecular insights into its mode(s) of action have been limited by an absence of structural data. Structural considerations along with a growing body of literature demonstrating its effects on one-carbon metabolism suggest the possibility of folate mimicry and anti-folate activity. Motivated by the growing recognition that anti-diabetic biguanides may act directly upon the gut microbiome, we have determined structures of the complexes formed between the anti-diabetic biguanides (phenformin, buformin, and metformin) and Escherichia coli dihydrofolate reductase (ecDHFR) based on nuclear magnetic resonance, crystallographic, and molecular modeling studies. Interligand Overhauser effects indicate that metformin can form ternary complexes with p-aminobenzoyl-l-glutamate (pABG) as well as other ligands that occupy the region of the folate-binding site that interacts with pABG; however, DHFR inhibition is not cooperative. The biguanides competitively inhibit the activity of ecDHFR, with the phenformin inhibition constant being 100-fold lower than that of metformin. This inhibition may be significant at concentrations present in the gut of treated individuals, and inhibition of DHFR in intestinal mucosal cells may also occur if accumulation levels are sufficient. Perturbation of folate homeostasis can alter the pyridine nucleotide redox ratios that are important regulators of cellular metabolism.
Topics: Biguanides; Binding Sites; Crystallization; Escherichia coli; Folic Acid Antagonists; Hypoglycemic Agents; Models, Molecular; Molecular Structure; Protein Conformation; Structure-Activity Relationship; Tetrahydrofolate Dehydrogenase
PubMed: 28766937
DOI: 10.1021/acs.biochem.7b00619 -
The Biochemical Journal Nov 2015Improvements in healthcare and nutrition have generated remarkable increases in life expectancy worldwide. This is one of the greatest achievements of the modern world... (Review)
Review
Improvements in healthcare and nutrition have generated remarkable increases in life expectancy worldwide. This is one of the greatest achievements of the modern world yet it also presents a grave challenge: as more people survive into later life, more also experience the diseases of old age, including type 2 diabetes (T2D), cardiovascular disease (CVD) and cancer. Developing new ways to improve health in the elderly is therefore a top priority for biomedical research. Although our understanding of the molecular basis of these morbidities has advanced rapidly, effective novel treatments are still lacking. Alternative drug development strategies are now being explored, such as the repurposing of existing drugs used to treat other diseases. This can save a considerable amount of time and money since the pharmacokinetics, pharmacodynamics and safety profiles of these drugs are already established, effectively enabling preclinical studies to be bypassed. Metformin is one such drug currently being investigated for novel applications. The present review provides a thorough and detailed account of our current understanding of the molecular pharmacology and signalling mechanisms underlying biguanide-protein interactions. It also focuses on the key role of the microbiota in regulating age-associated morbidities and a potential role for metformin to modulate its function. Research in this area holds the key to solving many of the mysteries of our current understanding of drug action and concerted effects to provide sustained and long-life health.
Topics: Biguanides; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Metformin; Neoplasms; Proteins
PubMed: 26475449
DOI: 10.1042/BJ20150497 -
Science (New York, N.Y.) Jan 2023The molecular mode of action of biguanides, including the drug metformin, which is widely used in the treatment of diabetes, is incompletely characterized. Here, we...
The molecular mode of action of biguanides, including the drug metformin, which is widely used in the treatment of diabetes, is incompletely characterized. Here, we define the inhibitory drug-target interaction(s) of a model biguanide with mammalian respiratory complex I by combining cryo-electron microscopy and enzyme kinetics. We interpret these data to explain the selectivity of biguanide binding to different enzyme states. The primary inhibitory site is in an amphipathic region of the quinone-binding channel, and an additional binding site is in a pocket on the intermembrane-space side of the enzyme. An independent local chaotropic interaction, not previously described for any drug, displaces a portion of a key helix in the membrane domain. Our data provide a structural basis for biguanide action and enable the rational design of medicinal biguanides.
Topics: Animals; Cryoelectron Microscopy; Electron Transport Complex I; Metformin; Mitochondria; Biguanides
PubMed: 36701435
DOI: 10.1126/science.ade3332 -
Skin Pharmacology and Physiology 2010
Topics: Anti-Infective Agents, Local; Antisepsis; Biguanides; Drug Resistance, Microbial; Humans; Skin; Wound Infection
PubMed: 20829655
DOI: 10.1159/000318899 -
BMC Medicine Apr 2011Biguanides have been developed for the treatment of hyperglycemia and type 2 diabetes. Recently, metformin, the most widely prescribed biguanide, has emerged as a... (Review)
Review
Biguanides have been developed for the treatment of hyperglycemia and type 2 diabetes. Recently, metformin, the most widely prescribed biguanide, has emerged as a potential anticancer agent. Epidemiological, preclinical and clinical evidence supports the use of metformin as a cancer therapeutic. The ability of metformin to lower circulating insulin may be particularly important for the treatment of cancers known to be associated with hyperinsulinemia, such as those of the breast and colon. Moreover, metformin may exhibit direct inhibitory effects on cancer cells by inhibiting mammalian target of rapamycin (mTOR) signaling and protein synthesis. The evidence supporting a role for metformin in cancer therapy and its potential molecular mechanisms of action are discussed.
Topics: Antineoplastic Agents; Drug Therapy, Combination; Humans; Metformin; Neoplasms
PubMed: 21470407
DOI: 10.1186/1741-7015-9-33 -
International Journal of Molecular... Mar 2023Metabolic reprogramming in cancer is considered to be one of the most important hallmarks to drive proliferation, angiogenesis, and invasion. AMP-activated protein...
Metabolic reprogramming in cancer is considered to be one of the most important hallmarks to drive proliferation, angiogenesis, and invasion. AMP-activated protein kinase activation is one of the established mechanisms for metformin's anti-cancer actions. However, it has been suggested that metformin may exert antitumoral effects by the modulation of other master regulators of cellular energy. Here, based on structural and physicochemical criteria, we tested the hypothesis that metformin may act as an antagonist of L-arginine metabolism and other related metabolic pathways. First, we created a database containing different L-arginine-related metabolites and biguanides. After that, comparisons of structural and physicochemical properties were performed employing different cheminformatic tools. Finally, we performed molecular docking simulations using AutoDock 4.2 to compare the affinities and binding modes of biguanides and L-arginine-related metabolites against their corresponding targets. Our results showed that biguanides, especially metformin and buformin, exhibited a moderate-to-high similarity to the metabolites belonging to the urea cycle, polyamine metabolism, and creatine biosynthesis. The predicted affinities and binding modes for biguanides displayed good concordance with those obtained for some L-arginine-related metabolites, including L-arginine and creatine. In conclusion, metabolic reprogramming in cancer cells by metformin and biguanides may be also driven by metabolic disruption of L-arginine and structurally related compounds.
Topics: Humans; Metformin; Molecular Docking Simulation; Creatine; Biguanides; AMP-Activated Protein Kinases; Buformin; Neoplasms; Antimalarials
PubMed: 36982390
DOI: 10.3390/ijms24065316 -
Molecules (Basel, Switzerland) Oct 2021The results presented in this paper confirm the beneficial role of an easy-to-use and low-cost thin-layer chromatography (TLC) technique for describing the retention... (Comparative Study)
Comparative Study
The results presented in this paper confirm the beneficial role of an easy-to-use and low-cost thin-layer chromatography (TLC) technique for describing the retention behavior and the experimental lipophilicity parameter of two biguanide derivatives, metformin and phenformin, in both normal-phase (NP) and reversed-phase (RP) TLC systems. The retention parameters (R, R) obtained under different chromatographic conditions, i.e., various stationary and mobile phases in the NP-TLC and RP-TLC systems, were used to determine the lipophilicity parameter (R) of metformin and phenformin. This study confirms the poor lipophilicity of both metformin and phenformin. It can be stated that the optimization of chromatographic conditions, i.e., the kind of stationary phase and the composition of mobile phase, was needed to obtain the reliable value of the chromatographic lipophilicity parameter (R) in this study. The fewer differences in the R values of both biguanide derivatives were ensured by the RP-TLC system composed of RP2, RP18, and RP18W plates and the mixture composed of methanol, propan-1-ol, and acetonitrile as an organic modifier compared to the NP-TLC analysis. The new calculation procedures for logP of drugs based on topological indices χ, χ, χ, M, and M may be a certain alternative to other algorithms as well as the TLC procedure performed under optimized chromatographic conditions. The knowledge of different lipophilicity parameters of the studied biguanides can be useful in the future design of novel and more therapeutically effective metformin and phenformin formulations for antidiabetic and possible anticancer treatment. Moreover, the topological indices presented in this work may be further used in the QSAR study of the examined biguanides.
Topics: Chromatography, Reverse-Phase; Chromatography, Thin Layer; Hydrophobic and Hydrophilic Interactions; Metformin; Molecular Structure; Phenformin
PubMed: 34771022
DOI: 10.3390/molecules26216613