scholarly journals Construction of a New Class of Tetracycline Lead Structures with Potent Antibacterial Activity through Biosynthetic Engineering

2015 ◽  
Vol 127 (13) ◽  
pp. 4009-4012 ◽  
Author(s):  
Urška Lešnik ◽  
Tadeja Lukežič ◽  
Ajda Podgoršek ◽  
Jaka Horvat ◽  
Tomaž Polak ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
New Class ◽  
Biosynthetic Engineering

scholarly journals Construction of a New Class of Tetracycline Lead Structures with Potent Antibacterial Activity through Biosynthetic Engineering

2015 ◽  
Vol 54 (13) ◽  
pp. 3937-3940 ◽  
Author(s):  
Urška Lešnik ◽  
Tadeja Lukežič ◽  
Ajda Podgoršek ◽  
Jaka Horvat ◽  
Tomaž Polak ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
New Class ◽  
Biosynthetic Engineering

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 Benzanthrins A and B, a new class of quinone antibiotics. I Discovery, fermentation and antibacterial activity.

1986 ◽  
Vol 39 (11) ◽  
pp. 1509-1514 ◽  
Author(s):  
ROBERT J. THERIAULT ◽  
RONALD R. RASMUSSEN ◽  
WILLIAM L. KOHL ◽  
JOSEPH F. PROKOP ◽  
THOMAS B. HUTCH ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
New Class

Improved supercapacitor potential and antibacterial activity of bimetallic CNFs–Sn–ZrO2 nanofibers: fabrication and characterization

RSC Advances ◽  
2014 ◽  
Vol 4 (33) ◽  
pp. 17268-17273 ◽  
Author(s):  
Young-Sang Jang ◽  
Touseef Amna ◽  
M. Shamshi Hassan ◽  
Ja-Lam Gu ◽  
Ick-Soo Kim ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
One Dimensional ◽  
New Class ◽  
Fabrication And Characterization

The objective of our study was to develop a new class of one-dimensional Sn–ZrO2 nanocrystal decorated CNFs.

scholarly journals N-Alkyl Urea Hydroxamic Acids as a New Class of Peptide Deformylase Inhibitors with Antibacterial Activity

2002 ◽  
Vol 46 (9) ◽  
pp. 2752-2764 ◽  
Author(s):  
Corinne J. Hackbarth ◽  
Dawn Z. Chen ◽  
Jason G. Lewis ◽  
Kirk Clark ◽  
James B. Mangold ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Antimicrobial Agents ◽  
Enzyme Inhibitor ◽  
Structural Information ◽  
Hydroxamic Acids ◽  
Parallel Synthesis ◽  
Peptide Deformylase ◽  
New Class ◽  
Relationship Analysis ◽  
Starting Point

ABSTRACT Peptide deformylase (PDF) is a prokaryotic metalloenzyme that is essential for bacterial growth and is a new target for the development of antibacterial agents. All previously reported PDF inhibitors with sufficient antibacterial activity share the structural feature of a 2-substituted alkanoyl at the P1′ site. Using a combination of iterative parallel synthesis and traditional medicinal chemistry, we have identified a new class of PDF inhibitors with N-alkyl urea at the P1′ site. Compounds with MICs of ≤4 μg/ml against gram-positive and gram-negative pathogens, including Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae, have been identified. The concentrations needed to inhibit 50% of enzyme activity (IC50s) for Escherichia coli Ni-PDF were ≤0.1 μM, demonstrating the specificity of the inhibitors. In addition, these compounds were very selective for PDF, with IC50s of consistently >200 μM for matrilysin and other mammalian metalloproteases. Structure-activity relationship analysis identified preferred substitutions resulting in improved potency and decreased cytotoxity. One of the compounds (VRC4307) was cocrystallized with PDF, and the enzyme-inhibitor structure was determined at a resolution of 1.7 Å. This structural information indicated that the urea compounds adopt a binding position similar to that previously determined for succinate hydroxamates. Two compounds, VRC4232 and VRC4307, displayed in vivo efficacy in a mouse protection assay, with 50% protective doses of 30.8 and 17.9 mg/kg of body weight, respectively. These N-alkyl urea hydroxamic acids provide a starting point for identifying new PDF inhibitors that can serve as antimicrobial agents.

ChemInform Abstract: A New Class of Fluoroquinolones: Benzenesulfonamidefluoroquinolones (BSFQs), Antibacterial Activity and SAR Studies.

ChemInform ◽  
2010 ◽  
Vol 30 (33) ◽  
pp. no-no
Author(s):  
Marcelo J. Nieto ◽  
Fabiana del Lujan Alovero ◽  
Ruben H. Manzo ◽  
Maria R. Mazzieri
Keyword(s):  
Antibacterial Activity ◽  
New Class ◽  
Sar Studies

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).

Sign in / Sign up

Export Citation Format

Share Document