Design, Synthesis and Antibacterial Activity screening of Novel Bis cyclic Imides Linked to Trimethoprim Drug

2021 ◽  
pp. 5874-5880
Author(s):  
Zaynab Hussein Fadel ◽  
Ahlam Marouf Al-Azzawi
Keyword(s):  
Bacterial Infections ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Building Blocks ◽  
Vital Role ◽  
High Biological Activity ◽  
Design Synthesis ◽  
Cyclic Imides ◽  
Tract Infections ◽  
Active Intermediates

Cyclic imides are well known important organic compounds that exhibit diverse biological activities like anti - inflammatory, antibacterial, analgesic, hypoglycemic and antifungal activities. Besides these compounds are useful building blocks in the synthesis of many drugs and pharmaceuticals. On the other hand trimethoprim is a well-known antibiotic that is used in combination with Sulfamethoxazole in treating urinary tract infections, bacterial infections and acute invasive diarrhea. Moreover Schiff bases represent the most active intermediates that exhibit wide spectrum of biological activities and play a vital role in the production of different pharmaceutical and bioactive heterocycles. Based on all these facts, it seems worthwhile to design and synthesize new molecules that contain these three active moieties (cyclic imide, trimethoprim and Schiff base) together in the same molecule since this may exhibit the new compounds high biological activity and may open possibilities for fighting bacterial infections.

An update on cefepime and its future role in combination with novel β-lactamase inhibitors for MDR Enterobacterales and Pseudomonas aeruginosa

2020 ◽  
Author(s):  
Burcu Isler ◽  
Patrick Harris ◽  
Adam G Stewart ◽  
David L Paterson
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Clinical Studies ◽  
Bacterial Infections ◽  
Animal Studies ◽  
Wide Spectrum ◽  
Clinical Development ◽  
Phase Iii ◽  
Lactam Antibiotic ◽  
Tract Infections

Abstract Cefepime, a wide-spectrum β-lactam antibiotic, has been in use for the treatment of serious bacterial infections for almost 25 years. Since its clinical development, there has been a dramatic shift in its dosing, with 2 g every 8 hours being preferred for serious infections to optimize pharmacokinetic/pharmacodynamic considerations. The advent of ESBLs has become a threat to its ongoing use, although future coadministration with β-lactamase inhibitors (BLIs) under development is an area of intense study. There are currently four new cefepime/BLI combinations in clinical development. Cefepime/zidebactam is generally active against MBL-producing Enterobacterales and Pseudomonas aeruginosa, in vitro and in animal studies, and cefepime/taniborbactam has activity against KPC and OXA-48 producers. Cefepime/enmetazobactam and cefepime/tazobactam are potential carbapenem-sparing agents with activity against ESBLs. Cefepime/enmetazobactam has completed Phase III and cefepime/taniborbactam is in Phase III clinical studies, where they are being tested against carbapenems or piperacillin/tazobactam for the treatment of complicated urinary tract infections. While these combinations are promising, their role in the treatment of MDR Gram-negative infections can only be determined with further clinical studies.

New Benzothiazole-based Thiazolidinones as Potent Antimicrobial Agents. Design, synthesis and Biological Evaluation

2018 ◽  
Vol 18 (1) ◽  
pp. 75-87 ◽  
Author(s):  
Michelyne Haroun ◽  
Christophe Tratrat ◽  
Katerina Kositzi ◽  
Evangelia Tsolaki ◽  
Anthi Petrou ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Agents ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Antimicrobial Properties ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Synthesis Methods ◽  
Design Synthesis ◽  
Benzothiazole Derivatives

Background: Thiazole and benzothiazole derivatives, as well as thiazolidinones are very important scaffolds in medicinal chemistry. Literature has revealed that they possess a wide spectrum of biological activities including antimicrobial activity. Objective: The goal of this paper is the designing of new benzothiazole based thiazolidinones and the evaluation of their biological activities. Methods: The designed compounds were synthesized using classical organic synthesis methods. The antimicrobial activity was evaluated using the method of microdilution. Results: The twelve newly synthesized compounds showed antimicrobial properties. All compounds appeared to be more active than ampicillin in most studied strains and in some cases, more active than streptomycin. Antifungal activity, in most cases was also better than the reference drugs ketoconazole and bifonazole. The prediction of cytotoxicity revealed that the synthesized compounds were not toxic (LD50 350-1000 mg/kg of body weight). Docking studies on the antibacterial activity confirmed the biological results. Conclusion: The twelve new compounds were synthesized and studied for their antimicrobial activity. The compounds appeared to be promising antimicrobial agents and could be the lead compounds for new, more potent drugs. According to the docking prediction, the compounds could be MurB inhibitors.

scholarly journals A small-molecular inhibitor against Proteus mirabilis urease to treat catheter-associated urinary tract infections

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Scarlet Milo ◽  
Rachel A. Heylen ◽  
John Glancy ◽  
George T. Williams ◽  
Bethany L. Patenall ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Proteus Mirabilis ◽  
Bacterial Infections ◽  
Competitive Inhibition ◽  
Enzyme Inhibitor ◽  
Urinary Catheters ◽  
Design Synthesis ◽  
In Silico Docking ◽  
Tract Infections

AbstractInfection and blockage of indwelling urinary catheters is significant owing to its high incidence rate and severe medical consequences. Bacterial enzymes are employed as targets for small molecular intervention in human bacterial infections. Urease is a metalloenzyme known to play a crucial role in the pathogenesis and virulence of catheter-associated Proteus mirabilis infection. Targeting urease as a therapeutic candidate facilitates the disarming of bacterial virulence without affecting bacterial fitness, thereby limiting the selective pressure placed on the invading population and lowering the rate at which it will acquire resistance. We describe the design, synthesis, and in vitro evaluation of the small molecular enzyme inhibitor 2-mercaptoacetamide (2-MA), which can prevent encrustation and blockage of urinary catheters in a physiologically representative in vitro model of the catheterized urinary tract. 2-MA is a structural analogue of urea, showing promising competitive activity against urease. In silico docking experiments demonstrated 2-MA’s competitive inhibition, whilst further quantum level modelling suggests two possible binding mechanisms.

scholarly journals Design, Synthesis and Antimicrobial Evaluation of New Norfloxacin-Naphthoquinone Hybrid Molecules

Proceedings ◽  
2019 ◽  
Vol 41 (1) ◽  
pp. 9 ◽  
Author(s):  
Andrea Defant ◽  
Alessandro Vozza ◽  
Ines Mancini
Keyword(s):  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Biological Activities ◽  
Dna Gyrase ◽  
Structural Features ◽  
Therapeutic Agents ◽  
Topoisomerase Iv ◽  
Design Synthesis ◽  
Biological Targets ◽  
Hybrid Molecules

Although the wide arsenal of drugs available to treat bacterial infections, emerging drug-resistant bacterial pathogens have recently highlighted an urgent need to find new more effective and less toxic therapeutic agents. Fluoroquinolones, including norfloxacin, are antibiotics showing a concentration-dependent bactericidal capacity due to the activity inhibition of DNA-gyrase and topoisomerase IV, which are enzymes essential for bacterial DNA replication. Naphthoquinones are secondary metabolites showing different biological activities, including cytotoxic, antibacterial and antifungal effects. In particular, the efficacy of natural and synthetic 1,4-naphthoquinone derivatives is likely due to their oxidizing/reducing capability, through which they destroy cellular targets as nucleic acids. Hybrid molecules are produced combining structural features of two or more bioactive compounds, in order to obtain new therapeutic agents able, not only to reduce undesirable side effects of the parent drugs, but also to inhibit more biological targets, hopefully with a better therapeutic property than the administration of combined single-target drugs. With the aim to apply this strategy in the study of new potential antimicrobial agents, we have synthesized four hybrid molecules by the reaction of norfloxacin with suitable quinones and their activities have been evaluated against both bacteria and fungi, in comparison with synthetic precursors. The experimental data are supported by docking calculations on S. aureus DNA-gyrase, discussing the interactions involved for each hybrid molecule, in comparison with norfloxacin and the original ligand moxifloxacin.

Recent Achievement in the Synthesis of Benzo[b]furans

2020 ◽  
Vol 17 (7) ◽  
pp. 498-517
Author(s):  
Dau Xuan Duc
Keyword(s):  
Organic Dyes ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Building Blocks ◽  
Future Application ◽  
Furan Derivative ◽  
Furan Derivatives ◽  
Electroluminescence Device ◽  
Drug Synthesis ◽  
New Methodologies

Background: Benzo[b]furan derivatives are oxygen-containing heterocyclic compounds consisting of fused benzene and furan rings and are present in a large number of natural and non-natural compounds. This class of compounds has a wide spectrum of biological activities, such as antiarrhythmic, anticancer, inflammatory, antioxidant, antimicrobial, and antiviral. Furthermore, benzo[b]furan derivatives have also been applied in various areas, such as organic electroluminescence device materials and organic dyes, photosensitizing material, organic synthesis as building blocks or intermediates. : Because of a broad range of applicability, the synthesis of benzo[b]furan derivative has drawn great attention of chemists and many studies on the synthesis of this class of compounds have been reported recently. This review will give an overview of benzo[b]furan preparation based on studies dating back to the year 2012. Objective: In this review, recent development in the synthesis of benzo[b]furans are discussed. There has been increasingly new methodologies for the construction of benzo[b]furans skeleton to improve efficiency or develop environmentally friendly procedures. In some studies, reaction mechanisms were also outlined. Conclusion: Many methods for the synthesis of benzo[b]furans have been reported recently. Most of them involve cyclization or cycloisomerization processes. Unquestionably, more imaginative strategies for the construction of benzo[b]furan skeleton will be established in the near future. Application of known methods to natural products or drug synthesis, on industrial scale for the synthesis of economically or medicinally important benzo[ b]furans will probably be paid attention to.

Synthesis of Pyrazole-Carboxamides and Pyrazole-Carboxylic Acids Derivatives: Simple Methods to Access Powerful Building Blocks

2020 ◽  
Vol 17 ◽  
Author(s):  
Byanca Silva Ferreira ◽  
Rafaela Corrêa Silva ◽  
Bernardo Araújo Souto ◽  
Maurício Silva dos Santos
Keyword(s):  
Hybrid Systems ◽  
Carboxylic Acids ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Pyrazole Ring ◽  
Building Blocks ◽  
Synthetic Methods

Abstract: Hybrid systems contained pyrazole moiety show a wide spectrum of biological activities. To access novel hybrids with pyrazole ring, in this work we synthesized twenty pyrazole-carboxylic acids and twenty pyrazole-carboxamides, using simple synthetic methods, to be used as building blocks in development of new structures

scholarly journals Imaging of Biliary Infections

2017 ◽  
Vol 01 (01) ◽  
pp. 003-007
Author(s):  
Ronald Arellano ◽  
Onofrio Catalano
Keyword(s):  
Infectious Diseases ◽  
Treatment Response ◽  
Biliary Tract ◽  
Wide Spectrum ◽  
Vital Role ◽  
Imaging Findings ◽  
Clinical Presentations ◽  
Tract Infections ◽  
Extent Of Disease

AbstractBiliary tract infections cover a wide spectrum of etiologies and clinical presentations. Imaging plays an important role in understanding the etiology and as well as the extent of disease. Imaging also plays a vital role in assessing treatment response once a diagnosis is established. This article will review the imaging findings of commonly encountered biliary tract infectious diseases.

Diverse chemical and biological potentials of various pyridazine and pyridazinone derivatives

2019 ◽  
Author(s):  
Chem Int
Keyword(s):  
Heterocyclic Compounds ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Biological Properties ◽  
Industrial Chemical ◽  
Anti Inflammatory ◽  
Pyridazinone Derivatives

A series of heterocyclic compounds incorporating pyridazine moiety were for diverse biological activities. Pyridazines and pyridazinones derivatives showed wide spectrum of biological activities such as vasodialator, cardiotonic, anticonvulsant, antihypertensive, antimicrobial, anti-inflammatory, analgesic, anti-feedant, herbicidal, and various other biological, agrochemical and industrial chemical activities. The results illustrated that the synthesized pyridazine/pyridazine compounds have diverse and significant biological activities. Mechanistic insights into the biological properties of pyridazinone derivatives and various synthetic techniques used for their synthesis are also described.

Sign in / Sign up

Export Citation Format

Share Document