scholarly journals Synthesis and Antibacterial Activity of Quaternary Ammonium 4-Deoxypyridoxine Derivatives

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Nikita V. Shtyrlin ◽  
Sergey V. Sapozhnikov ◽  
Albina S. Galiullina ◽  
Airat R. Kayumov ◽  
Oksana V. Bondar ◽  
...  
Keyword(s):  
Quaternary Ammonium ◽  
Benzalkonium Chloride ◽  
Ames Test ◽  
Kidney Cells ◽  
Mutagenic Potential ◽  
E Coli ◽  
Sos Chromotest ◽  
Cytotoxicity Studies ◽  
Starting Point ◽  
Excellent Activity

A series of novel quaternary ammonium 4-deoxypyridoxine derivatives was synthesized. Two compounds demonstrated excellent activity against a panel of Gram-positive methicillin-resistantS. aureusstrains with MICs in the range of 0.5–2 μg/mL, exceeding the activity of miramistin. At the same time, both compounds were inactive against the Gram-negativeE. coliandP. aeruginosastrains. Cytotoxicity studies on human skin fibroblasts and embryonic kidney cells demonstrated that the active compounds possessed similar toxicity with benzalkonium chloride but were slightly more toxic than miramistin. SOS-chromotest inS. typhimuriumshowed the lack of DNA-damage activity of both compounds; meanwhile, one compound showed some mutagenic potential in the Ames test. The obtained results make the described chemotype a promising starting point for the development of new antibacterial therapies.

scholarly journals Genotoxicity of Some Metal-Based Antineoplastics, Evaluated by SOS Chromotest and Cytogenetic Analysis

1996 ◽  
Vol 3 (2) ◽  
pp. 91-99 ◽  
Author(s):  
Carmen Socaciu ◽  
Loan Pasca ◽  
Cristian Silvestru ◽  
Ionel Haiduc
Keyword(s):  
Chromosomal Aberrations ◽  
Cytogenetic Analysis ◽  
Positive Response ◽  
Metabolic Activation ◽  
Antineoplastic Drugs ◽  
Mutagenic Potential ◽  
E Coli ◽  
Bacterial Cultures ◽  
Sos Chromotest ◽  
Clastogenic Effect

The paper reports the screening results of two metal-based antineoplastic drugs with mutagenic potential, such as Romcis (trademark of Cisplatinum, produced in Romania) and diphenylantimony(III) diisopropyldithiophosphate (PADTF). Their effects were compared with those induced by Cyclophosphamide. Two mutagenicity tests, the SOS Chromotest and cytogenetic analysis were applied. The tests were carried out with or without metabolic activation (addition of S9-mix), either in E. coli PQ 37 cultures, using four doses (0.3, 3, 30 and 300 pmol compound/assay) for the SOS Chromotest or in leukocyte cultures using 0.3 mM from each compound, for cytogenetics. The dose- response relationships and SOSIP values revealed an indirect mutagenic potential for Cyclophosphamide, amplified by S9 mix in bacterial cultures and an antiproliferative, clastogenic effect on lymphocytes. For Romcis and diphenylantimony(III) diisopropyldithiophosphate, a significant positive response by SOS Chromotest was recorded, which correlated with increased frequencies of chromosomal aberrations.

Identification of N-Substituted Triazolo-azetidines as Novel Antibacterials using pDualrep2 HTS Platform

2019 ◽  
Vol 22 (5) ◽  
pp. 346-354
Author(s):  
Yan A. Ivanenkov ◽  
Renat S. Yamidanov ◽  
Ilya A. Osterman ◽  
Petr V. Sergiev ◽  
Vladimir A. Aladinskiy ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Large Scale ◽  
Underlying Mechanism ◽  
Luciferase Assay ◽  
Reporter System ◽  
E Coli ◽  
Starting Point ◽  
High Concentrations ◽  
Mic Value

Aim and Objective: Antibiotic resistance is a serious constraint to the development of new effective antibacterials. Therefore, the discovery of the new antibacterials remains one of the main challenges in modern medicinal chemistry. This study was undertaken to identify novel molecules with antibacterial activity. Materials and Methods: Using our unique double-reporter system, in-house large-scale HTS campaign was conducted for the identification of antibacterial potency of small-molecule compounds. The construction allows us to visually assess the underlying mechanism of action. After the initial HTS and rescreen procedure, luciferase assay, C14-test, determination of MIC value and PrestoBlue test were carried out. Results: HTS rounds and rescreen campaign have revealed the antibacterial activity of a series of Nsubstituted triazolo-azetidines and their isosteric derivatives that has not been reported previously. Primary hit-molecule demonstrated a MIC value of 12.5 µg/mL against E. coli Δ tolC with signs of translation blockage and no SOS-response. Translation inhibition (26%, luciferase assay) was achieved at high concentrations up to 160 µg/mL, while no activity was found using C14-test. The compound did not demonstrate cytotoxicity in the PrestoBlue assay against a panel of eukaryotic cells. Within a series of direct structural analogues bearing the same or bioisosteric scaffold, compound 2 was found to have an improved antibacterial potency (MIC=6.25 µg/mL) close to Erythromycin (MIC=2.5-5 µg/mL) against the same strain. In contrast to the parent hit, this compound was more active and selective, and provided a robust IP position. Conclusion: N-substituted triazolo-azetidine scaffold may be used as a versatile starting point for the development of novel active and selective antibacterial compounds.

scholarly journals Polyphenylglyoxamide-Based Amphiphilic Small Molecular Peptidomimetics as Antibacterial Agents with Anti-Biofilm Activity

2021 ◽  
Vol 22 (14) ◽  
pp. 7344
Author(s):  
Tsz Tin Yu ◽  
Rajesh Kuppusamy ◽  
Muhammad Yasir ◽  
Md. Musfizur Hassan ◽  
Manjulatha Sara ◽  
...  
Keyword(s):  
Quaternary Ammonium ◽  
Antibacterial Agents ◽  
Health Concern ◽  
Resistant Bacteria ◽  
Ammonium Iodide ◽  
E Coli ◽  
Drug Resistant Bacteria ◽  
Permeability Study ◽  
Cationic Group ◽  
Chain Lengths

The rapid emergence of drug-resistant bacteria is a major global health concern. Antimicrobial peptides (AMPs) and peptidomimetics have arisen as a new class of antibacterial agents in recent years in an attempt to overcome antibiotic resistance. A library of phenylglyoxamide-based small molecular peptidomimetics was synthesised by incorporating an N-alkylsulfonyl hydrophobic group with varying alkyl chain lengths and a hydrophilic cationic group into a glyoxamide core appended to phenyl ring systems. The quaternary ammonium iodide salts 16d and 17c showed excellent minimum inhibitory concentration (MIC) of 4 and 8 μM (2.9 and 5.6 μg/mL) against Staphylococcus aureus, respectively, while the guanidinium hydrochloride salt 34a showed an MIC of 16 μM (8.5 μg/mL) against Escherichia coli. Additionally, the quaternary ammonium iodide salt 17c inhibited 70% S. aureus biofilm formation at 16 μM. It also disrupted 44% of pre-established S. aureus biofilms at 32 μM and 28% of pre-established E. coli biofilms 64 μM, respectively. A cytoplasmic membrane permeability study indicated that the synthesised peptidomimetics acted via disruption and depolarisation of membranes. Moreover, the quaternary ammonium iodide salts 16d and 17c were non-toxic against human cells at their therapeutic dosages against S. aureus.

scholarly journals Synthesis, Antimicrobial Activity and Molecular Docking of Novel Thiourea Derivatives Tagged with Thiadiazole, Imidazole and Triazine Moieties as Potential DNA Gyrase and Topoisomerase IV Inhibitors

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2766 ◽  
Author(s):  
Heba E. Hashem ◽  
Abd El-Galil E. Amr ◽  
Eman S. Nossier ◽  
Elsayed A. Elsayed ◽  
Eman M. Azmy
Keyword(s):  
Antimicrobial Activity ◽  
Molecular Docking ◽  
Antimicrobial Agents ◽  
Biological Activities ◽  
Topoisomerase Iv ◽  
Thiourea Derivatives ◽  
E Coli ◽  
Cytotoxicity Studies ◽  
Ic50 Values

To develop new antimicrobial agents, a series of novel thiourea derivatives incorporated with different moieties 2–13 was designed and synthesized and their biological activities were evaluated. Compounds 7a, 7b and 8 exhibited excellent antimicrobial activity against all Gram-positive and Gram-negative bacteria, and the fungal Aspergillus flavus with minimum inhibitory concentration (MIC) values ranged from 0.95 ± 0.22 to 3.25 ± 1.00 μg/mL. Furthermore, cytotoxicity studies against MCF-7 cells revealed that compounds 7a and 7b were the most potent with IC50 values of 10.17 ± 0.65 and 11.59 ± 0.59 μM, respectively. On the other hand, the tested compounds were less toxic against normal kidney epithelial cell lines (Vero cells). The in vitro enzyme inhibition assay of 8 displayed excellent inhibitory activity against Escherichia coli DNA B gyrase and moderate one against E. coli Topoisomerase IV (IC50 = 0.33 ± 1.25 and 19.72 ± 1.00 µM, respectively) in comparison with novobiocin (IC50 values 0.28 ± 1.45 and 10.65 ± 1.02 µM, respectively). Finally, the molecular docking was done to position compound 8 into the E. coli DNA B and Topoisomerase IV active pockets to explore the probable binding conformation. In summary, compound 8 may serve as a potential dual E. coli DNA B and Topoisomerase IV inhibitor.

Antibacterial Activity of Reactive Quaternary Ammonium Compounds in Solution and in Nonleachable Coatings

2011 ◽  
Vol 74 (12) ◽  
pp. 2107-2112 ◽  
Author(s):  
G. GOZZELINO ◽  
D. E. ROMERO TOBAR ◽  
N. CHAITIEMWONG ◽  
W. HAZELEGER ◽  
R. BEUMER
Keyword(s):  
Stainless Steel ◽  
Quaternary Ammonium ◽  
Acrylic Resin ◽  
Maximum Activity ◽  
E Coli ◽  
Alkyl Chains ◽  
Acrylic Resins ◽  
Antibacterial Polymers ◽  
Order Of Magnitude ◽  
Free Films

Antibacterial polymers suitable for coating applications without leaching of the biocidal component have been obtained by UV copolymerization of acrylic resins with acrylic monomers containing quaternary ammonium moieties. Suitable reactive biocides, based on quaternary ammonium monomers (QAMs), endowed with undecylacryloyl group and alkyl chains with 2 (QAM-C2), 8 (QAM-C8), and 16 (QAM-C16) carbon atoms have been synthesized. Aqueous solutions of QAMs showed biocidal activity against Escherichia coli, Staphylococcus aureus, and Listeria monocytogenes strains both in suspension and adhered to stainless steel surfaces. QAM-C16 and QAM-C8 evidenced higher activity toward bacteria in suspension and on stainless steel, respectively. The QAMs have shown sufficient reactivity to be copolymerized, by UV irradiation, with a commercial urethane acrylic resin for coating. Bioactivity tests, performed on free films of crosslinked coatings containing 1% of copolymerized QAM, have shown an increasing inactivation effect in the order of magnitude L. monocytogenes < E. coli < S. aureus with a maximum activity of the QAM-C8.

scholarly journals Protegrin-1 Inhibits Dengue NS2B-NS3 Serine Protease and Viral Replication in MK2 Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Hussin A. Rothan ◽  
Ammar Y. Abdulrahman ◽  
Pottayil G. Sasikumer ◽  
Shatrah Othman ◽  
Noorsaadah Abd Rahman ◽  
...  
Keyword(s):  
Viral Replication ◽  
Therapeutic Potential ◽  
Solid Phase ◽  
Dengue Infection ◽  
Solid Phase Peptide Synthesis ◽  
Single Chain ◽  
E Coli ◽  
Social Burden ◽  
Disulphide Bonds ◽  
Starting Point

Dengue diseases have an economic as well as social burden worldwide. In this study, the antiviral activity of protegrin-1 (PG-1, RGGRLCYCRRRFCVCVGR) peptide towards dengue NS2B-NS3pro and viral replication in Rhesus monkey kidney (MK2) cells was investigated. The peptide PG-1 was synthesized by solid-phase peptide synthesis, and disulphide bonds formation followed by peptide purification was confirmed by LC-MS and RPHPLC. Dengue NS2B-NS3pro was produced as a single-chain recombinant protein inE. coli. The NS2B-NS3pro assay was carried out by measuring the florescence emission of catalyzed substrate. Real-time PCR was used to evaluate the inhibition potential of PG-1 towards dengue serotype-2 (DENV-2) replication in MK2 cells. The results showed that PG-1 inhibited dengue NS2B-NS3pro at IC50of 11.7 μM. The graded concentrations of PG-1 at nontoxic range were able to reduce viral replication significantly (P<0.001) at 24, 48, and 72 hrs after viral infection. However, the percentage of inhibition was significantly (P<0.01) higher at 24 hrs compared to 48 and 72 hrs. These data show promising therapeutic potential of PG-1 against dengue infection, hence it warrants further analysis and improvement of the peptide features as a prospective starting point for consideration in designing attractive dengue virus inhibitors.

scholarly journals A Promising Copper(II) Complex as Antifungal and Antibiofilm Drug against Yeast Infection

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 1856 ◽  
Author(s):  
Fabiana Gomes da Silva Dantas ◽  
Adriana Araújo de Almeida-Apolonio ◽  
Renata Pires de Araújo ◽  
Lis Regiane Vizolli Favarin ◽  
Pamella Fukuda de Castilho ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Ames Test ◽  
Inhibitory Concentration ◽  
Coordination Complexes ◽  
Antifungal Property ◽  
Candida Spp ◽  
Mutagenic Potential ◽  
Yeast Infection ◽  
Limited Option ◽  
Potential Complex

The high mortality rate of candidemia and the limited option for the treatment of Candida spp. infection have been driving the search for new molecules with antifungal property. In this context, coordination complexes of metal ions and ligands appear to be important. Therefore, this study aimed to synthesize two new copper(II) complexes with 2-thiouracil and 6-methyl-2-thiouracil ligands and to evaluate their mutagenic potential and antifungal activity against Candida. The complexes were synthesized and characterized by infrared vibrational spectroscopy, CHN elemental analysis, UV-Vis experiments and ESI-HRMS spectrometry studies. The antifungal activity was evaluated by broth microdilution against 21 clinical isolates of Candida species. The mutagenic potential was evaluated by the Ames test. The complexes were Cu(Bipy)Cl2(thiouracil) (Complex 1) and Cu(Bipy)Cl2(6-methylthiouracil) (Complex 2). Complex 1 showed fungicidal and fungistatic activities against all isolates. Furthermore, the Minimum Inhibitory Concentration (MIC) from 31 to 125 µg/mL and inhibition percentage of 9.9% against the biofilms of C. krusei and C. glabrata were demonstrated. At the concentrations tested, complex 1 exhibited no mutagenic potential. Complex 2 and the free ligands exhibited no antifungal activity at the concentrations evaluated. Since complex 1 presented antifungal activity against all the tested isolates and no mutagenic potential, it could be proposed as a potential new drug for anti-Candida therapy.

INFLUENCE OF ORGANIC MATTER ON THE GERMICIDAL EFFICIENCY OF QUATERNARY AMMONIUM AND HYPOCHLORITE COMPOUNDS

1948 ◽  
Vol 26f (2) ◽  
pp. 91-104 ◽  
Author(s):  
C. K. Johns
Keyword(s):  
Staphylococcus Aureus ◽  
Organic Matter ◽  
Quaternary Ammonium ◽  
Tap Water ◽  
Skim Milk ◽  
Distilled Water ◽  
Water Solutions ◽  
E Coli ◽  
Test Organisms ◽  
High Concentrations

Using Staphylococcus aureus and Eschericha coli as test organisms, the influence of various concentrations of skim milk on the germicidal potency of Roccal and of Dalglish hypochlorite solutions was studied. Both germicides retained their activity in the presence of unexpectedly high concentrations of skim milk, especially against S. aureus. Small concentrations frequently showed a slight potentiating effect in both laboratory and plant tests. The effectiveness of the hypochlorite fell off sharply beyond a certain concentration, while that of Roccal declined more gradually. Solutions of Roccal prepared with tap water were decidedly less active against E. coli than those prepared with distilled water. With the hypochlorite, tap water solutions were equally effective. Against S. aureus, a similar difference was noted although to a lesser extent. Added skim milk depressed the germicidal action of tap water solutions of Roccal to a greater extent than for distilled water solutions, while for the hypochlorite the reverse held true.

Sign in / Sign up

Export Citation Format

Share Document