3-Aminoquinazolinediones as a New Class of Antibacterial Agents Demonstrating Excellent Antibacterial Activity Against Wild-Type and Multidrug Resistant Organisms

2006 ◽  
Vol 49 (22) ◽  
pp. 6435-6438 ◽  
Author(s):  
Edmund L. Ellsworth ◽  
Tuan P. Tran ◽  
H. D. Hollis Showalter ◽  
Joseph P. Sanchez ◽  
Brian M. Watson ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Antibacterial Agents ◽  
Multidrug Resistant ◽  
Wild Type ◽  
New Class ◽  
Multidrug Resistant Organisms

Large-scale High-throughput Screening Revealed 5'-(carbonylamino)-2,3'- bithiophene-4'-carboxylate as Novel Template for Antibacterial Agents

2020 ◽  
Vol 17 (5) ◽  
pp. 716-724
Author(s):  
Yan A. Ivanenkov ◽  
Renat S. Yamidanov ◽  
Ilya A. Osterman ◽  
Petr V. Sergiev ◽  
Vladimir A. Aladinskiy ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
High Throughput ◽  
High Throughput Screening ◽  
Large Scale ◽  
Antibacterial Agents ◽  
Sos Response ◽  
Luciferase Assay ◽  
Translational Machinery ◽  
E Coli ◽  
New Class

Background: The key issue in the development of novel antimicrobials is a rapid expansion of new bacterial strains resistant to current antibiotics. Indeed, World Health Organization has reported that bacteria commonly causing infections in hospitals and in the community, e.g. E. Coli, K. pneumoniae and S. aureus, have high resistance vs the last generations of cephalosporins, carbapenems and fluoroquinolones. During the past decades, only few successful efforts to develop and launch new antibacterial medications have been performed. This study aims to identify new class of antibacterial agents using novel high-throughput screening technique. Methods: We have designed library containing 125K compounds not similar in structure (Tanimoto coeff.< 0.7) to that published previously as antibiotics. The HTS platform based on double reporter system pDualrep2 was used to distinguish between molecules able to block translational machinery or induce SOS-response in a model E. coli system. MICs for most active chemicals in LB and M9 medium were determined using broth microdilution assay. Results: In an attempt to discover novel classes of antibacterials, we performed HTS of a large-scale small molecule library using our unique screening platform. This approach permitted us to quickly and robustly evaluate a lot of compounds as well as to determine the mechanism of action in the case of compounds being either translational machinery inhibitors or DNA-damaging agents/replication blockers. HTS has resulted in several new structural classes of molecules exhibiting an attractive antibacterial activity. Herein, we report as promising antibacterials. Two most active compounds from this series showed MIC value of 1.2 (5) and 1.8 μg/mL (6) and good selectivity index. Compound 6 caused RFP induction and low SOS response. In vitro luciferase assay has revealed that it is able to slightly inhibit protein biosynthesis. Compound 5 was tested on several archival strains and exhibited slight activity against gram-negative bacteria and outstanding activity against S. aureus. The key structural requirements for antibacterial potency were also explored. We found, that the unsubstituted carboxylic group is crucial for antibacterial activity as well as the presence of bulky hydrophobic substituents at phenyl fragment. Conclusion: The obtained results provide a solid background for further characterization of the 5'- (carbonylamino)-2,3'-bithiophene-4'-carboxylate derivatives discussed herein as new class of antibacterials and their optimization campaign.

Recent Advances in 1,3,5-Triazine Derivatives as Antibacterial Agents

2020 ◽  
Vol 17 (8) ◽  
pp. 991-1041
Author(s):  
Divya Utreja ◽  
Jagdish Kaur ◽  
Komalpreet Kaur ◽  
Palak Jain
Keyword(s):  
Antibacterial Activity ◽  
Heterocyclic Compounds ◽  
Antibacterial Agents ◽  
Rapid Development ◽  
Pharmacological Action ◽  
Biological Properties ◽  
Vast Array ◽  
Bacterial Diseases ◽  
New Class ◽  
Triazine Derivatives

Triazine, one of the nitrogen containing heterocyclic compounds has attracted the considerable interest of researchers due to the vast array of biological properties such as anti-viral, antitumor, anti-convulsant, analgesic, antioxidant, anti-depressant, herbicidal, insecticidal, fungicidal, antibacterial and anti-inflammatory activities offered by it. Various antibacterial agents have been synthesized by researchers to curb bacterial diseases but due to rapid development in drug resistance, tolerance and side effects, there had always been a need for the synthesis of a new class of antibacterial agents that would exhibit improved pharmacological action. Therefore, this review mainly focuses on the various methods for the synthesis of triazine derivatives and their antibacterial activity.

scholarly journals Cyathea gigantea (Cyatheaceae) as an antimicrobial agent against multidrug resistant organisms

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Kathakali Nath ◽  
Anupam Das Talukdar ◽  
Mrinal Kanti Bhattacharya ◽  
Deepshikha Bhowmik ◽  
Shiela Chetri ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Antibacterial Property ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Diffusion Method ◽  
Synergistic Activity ◽  
Gram Positive ◽  
Traditional Use ◽  
Gram Negative ◽  
Multidrug Resistant Organisms

Abstract Background Rapid emergence of multidrug resistant (MDR) organisms in hospital and community settings often result into treatment failure, thus leading the clinicians with fewer treatment options. Cyathea gigantea, an ethnomedicinally important fern used in cuts and wound infections. So, if this medicinal plant is used in treating the MDR infections then it might bring certain relief in future treatment options. Methods Antibacterial activity of C. gigantea against MDR bacteria was assed using well diffusion and broth microdilution methods to determine the diameters of growth inhibition zones, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Synergistic activity was also determined with the conventional antibiotics by disc diffusion method followed by FIC index of each of the tested antibiotic was calculated. The active extract was then subjected to fractionation by column chromatography and antibacterial activity was done with each of the collected fractions. Results Crude extract of C. gigantea was found to be active against all the tested organisms. The MIC was 200 μg/ml against Gram-positive i.e., Staphylococcus aureus ATCC 25923 and 400 μg/ml against Gram-negative i.e., Escherichia coli ATCC 25922 and Pseudomonas aeruginosa PAO1, while the MBC was 400 μg/ml in case of Gram-positive and 800 μg/ml for Gram-negative. The synergistic activity revealed that the plant extract increased the antibacterial property of the studied antibiotics and the FIC index showed that significant synergistic activity was shown by ciprofloxacin followed by tetracycline, ampicillin and oxacillin. Antibacterial activity with the fractionated extract showed that the FR II, FR III and FR IV were active against both Gram-positive and Gram-negative bacteria, whereas FR I, FR V and FR VI did not show antibacterial property against any of the tested bacteria. Conclusions Extracts of C. gigantea was found active against both selected Gram-positive and Gram-negative organisms and thus offers the scientific basis for the traditional use of the fern. The present study also provides the basis for future study to validate the possible use against multidrug resistant organisms.

scholarly journals A Novel Cecropin D-Derived Short Cationic Antimicrobial Peptide Exhibits Antibacterial Activity Against Wild-Type and Multidrug-Resistant Strains of Klebsiella pneumoniae and Pseudomonas aeruginosa

2020 ◽  
Vol 16 ◽  
pp. 117693432093626
Author(s):  
Iván Darío Ocampo-Ibáñez ◽  
Yamil Liscano ◽  
Sandra Patricia Rivera-Sánchez ◽  
José Oñate-Garzón ◽  
Ashley Dayan Lugo-Guevara ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibacterial Activity ◽  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Health Concern ◽  
Wild Type ◽  
Cationic Antimicrobial Peptide ◽  
Promising Alternative ◽  
Resistant Strains

Infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa and Klebsiella pneumoniae are a serious worldwide public health concern due to the ineffectiveness of empirical antibiotic therapy. Therefore, research and the development of new antibiotic alternatives are urgently needed to control these bacteria. The use of cationic antimicrobial peptides (CAMPs) is a promising candidate alternative therapeutic strategy to antibiotics because they exhibit antibacterial activity against both antibiotic susceptible and MDR strains. In this study, we aimed to investigate the in vitro antibacterial effect of a short synthetic CAMP derived from the ΔM2 analog of Cec D-like (CAMP-CecD) against clinical isolates of K pneumoniae (n = 30) and P aeruginosa (n = 30), as well as its hemolytic activity. Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of CAMP-CecD against wild-type and MDR strains were determined by the broth microdilution test. In addition, an in silico molecular dynamic simulation was performed to predict the interaction between CAMP-CecD and membrane models of K pneumoniae and P aeruginosa. The results revealed a bactericidal effect of CAMP-CecD against both wild-type and resistant strains, but MDR P aeruginosa showed higher susceptibility to this peptide with MIC values between 32 and >256 μg/mL. CAMP-CecD showed higher stability in the P aeruginosa membrane model compared with the K pneumoniae model due to the greater number of noncovalent interactions with phospholipid 1-Palmitoyl-2-oleyl-sn-glycero-3-(phospho-rac-(1-glycerol)) (POPG). This may be related to the boosted effectiveness of the peptide against P aeruginosa clinical isolates. Given the antibacterial activity of CAMP-CecD against wild-type and MDR clinical isolates of P aeruginosa and K pneumoniae and its nonhemolytic effects on human erythrocytes, CAMP-CecD may be a promising alternative to conventional antibiotics.

scholarly journals Challenges and Solutions for Clinical Development of New Antibacterial Agents: Results of a Survey among Pharmaceutical Industry Professionals

2015 ◽  
Vol 59 (7) ◽  
pp. 3695-3699 ◽  
Author(s):  
Esther Bettiol ◽  
Jeffrey D. Wetherington ◽  
Nicola Schmitt ◽  
Stephan Harbarth
Keyword(s):  
Pharmaceutical Industry ◽  
Diagnostic Tests ◽  
Antibacterial Agents ◽  
Multidrug Resistant ◽  
Rapid Diagnostic Tests ◽  
Clinical Development ◽  
Regulatory Guidance ◽  
Multidrug Resistant Organisms ◽  
Industry Professionals

ABSTRACTAs the number of antibacterial medicines in the pipeline remains low, we anonymously surveyed pharmaceutical industry professionals on challenges and solutions for clinical development of these agents. Challenges were reported primarily as financial and regulatory. For multidrug-resistant organisms, there are needs for rapid diagnostic tests, new regulatory guidance, and adaptation of endpoints/trial designs. Regulators and public/private initiatives are addressing these challenges to help ensure that proposed solutions have the support of all involved stakeholders.

Synthesis of Fluorinated Piperazinyl Substituted Quinazolines as Potential Antibacterial Agents

2020 ◽  
Vol 5 (3) ◽  
pp. 227-233
Author(s):  
Amit B. Patel ◽  
Purvesh Patel ◽  
Kajal Patel ◽  
Krupa Prajapati
Keyword(s):  
Antibacterial Activity ◽  
13C Nmr ◽  
Antibacterial Agents ◽  
Multidrug Resistant ◽  
Biological Species ◽  
Piperazine Ring ◽  
Minimum Inhibitory Concentrations ◽  
Ft Ir ◽  
Resistant Strains ◽  
Quinazoline Derivatives

In present study, fluorinated piperazine and benzonitrile/nicotinonitrile fused quinazoline derivatives have synthesized, characterized using FT-IR, 1H & 13C NMR, 19F NMR and MS analysis and evaluated as potential antibacterial agents. They were also tested against the multidrug resistant strains. The antibacterial activity results revealed that the majority of synthesized compounds exhibited potential antibacterial with the extraordinary level of minimum inhibitory concentrations comparable to the control drugs. Moreover, the influence of presence or absence of fluoro and trifluoromethyl functional groups on the piperazine ring systems towards different biological species is elaborated. The synthesized compounds were also found non-toxic on the human cervical (HeLa) cells at their minimum inhibitory concentrations.

scholarly journals 1,4-Naphthoquinone Analogues: Potent Antibacterial Agents and Mode of Action Evaluation

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1437 ◽  
Author(s):  
Palanisamy Ravichandiran ◽  
Sunirmal Sheet ◽  
Dhanraj Premnath ◽  
Ae Rhan Kim ◽  
Dong Jin Yoo
Keyword(s):  
Antibacterial Activity ◽  
Mode Of Action ◽  
Bacterial Infections ◽  
Antibacterial Agents ◽  
Annexin V ◽  
Ros Generation ◽  
Redox Potentials ◽  
Bacterial Strains ◽  
E Coli ◽  
New Class

1,4-Naphthoquinones have antibacterial activity and are a promising new class of compound that can be used to treat bacterial infections. The goal was to improve effective antibacterial agents; therefore, we synthesized a new class of naphthoquinone hybrids, which contain phenylamino-phenylthio moieties as significant counterparts. Compound 4 was modified as a substituted aryl amide moiety, which enhanced the antibacterial activity of earlier compounds 3 and 4. In this study, five bacterial strains Staphylococcus aureus (S. aureus), Listeria monocytogenes (L. monocytogenes), Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa) and Klebsiella pneumoniae (K. pneumoniae) were used to evaluate the antibacterial potency of synthesized naphthoquinones using the minimal inhibitory concentration (MIC) method. Most of the studied naphthoquinones demonstrated major antibacterial activity with a MIC of 15.6 µg/mL–500 µg/mL. Selected compounds (5a, 5f and 5x) were studied for the mode of action, using intracellular ROS generation, determination of apoptosis by the Annexin V-FITC/PI assay, a bactericidal kinetic study and in silico molecular modelling. Additionally, the redox potentials of the specified compounds were confirmed by cyclic voltammetry (CV).

scholarly journals Broad Spectrum Antibacterial Ocotillol-Type Derivatives: Semi-Synthesis, Structure-Activity Relationship, and Membrane-Active Mode of Action

2021 ◽  
Author(s):  
Xianming Zeng ◽  
Ziyi Zhang ◽  
Yunyun Zhou ◽  
Shengyu Zhang ◽  
Zhiwen Zhou
Keyword(s):  
Antibacterial Activity ◽  
Antibacterial Agents ◽  
Bacterial Resistance ◽  
Synergistic Effects ◽  
Resistance Mechanism ◽  
Multidrug Resistant ◽  
Hek 293 ◽  
Low Cytotoxicity ◽  
New Compounds

A series of 3-amino substituted ocotillol-type derivatives were designed and synthesized for the first time. The in vitro antibacterial activity tests showed that some of the new compounds exhibited excellent antibacterial activity. Compound 13d, which was the most active one, displayed particularly strong antibacterial activity against S. aureus, B. subtilis, MRSA (methicillin-resistant S. aureus) and E. coli with minimum inhibitory concentration (MIC) values of 1-4 μg mL-1. Further research also suggested that 13d showed low cytotoxicity to human normal cells HEK-293 and L02, strong synergistic effects with kanamycin or chloramphenicol and a broad antibacterial spectrum including against multidrug-resistant strains. This active molecule 13d also induced bacterial resistance more slowly than norfloxacin and colistin. Furthermore, the research results demonstrated that this type of compounds could disperse the established bacterial biofilms, thus suppressing or delaying the development of drug resistance. Mechanism studies have shown that compound 13d could damage the integrity of cell membranes, which in turn facilitated the antibacterial agents binding to deoxyribonucleic acid (DNA), leading to cell death. Therefore, these results indicated that the membrane active ocotillol-type derivatives are a promising class of antibacterial agents to fight against super bacteria and deserve further attention.

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