scholarly journals Design, Synthesis and In Vitro Antimicrobial Activity of 6-(1H-Benzimidazol-2-yl)-3,5-dimethyl-4-oxo-2-thio-3,4-dihydrothieno[2,3-d]pyrimidines

2021 ◽  
Vol 89 (4) ◽  
pp. 49
Author(s):  
Sergiy V. Vlasov ◽  
Olena D. Vlasova ◽  
Hanna I. Severina ◽  
Konstantin Y. Krolenko ◽  
Oleksandr V. Borysov ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Carboxylic Acid ◽  
Bacterial Resistance ◽  
Rapid Development ◽  
Antimicrobial Properties ◽  
Docking Studies ◽  
Antibacterial Drug ◽  
Design Synthesis ◽  
Drug Candidates

The rapid development in bacterial resistance to many groups of known antibiotics forces the researchers to discover antibacterial drug candidates with previously unknown mechanisms of action, one of the most relevant being the inhibition of tRNA (Guanine37-N1)-methyltransferase (TrmD). The discovery of selective TrmD inhibitors in the series of carboxamide derivatives of thienopyrimidines became a background for further modification of the similar structures aimed at the development of promising antibacterial agents. As part of this research, we carried out the construction of heterocyclic hybrids bearing the moieties of thieno[2,3-d]pyrimidine and benzimidazole starting from 3,5-dimethyl-4-oxo-2-thioxo-1H-thieno[2,3-d]pyrimidine-6-carboxylic acid, which was used as the pivotal intermediate. The hybrid molecule of 6-(1H-benzimidazol-2-yl)-3,5-dimethyl-2-thioxo-1H-thieno[2,3-d]pyrimidin-4-one prepared via condensation of the carboxylic acid with ortho-phenylenediamine was further alkylated with aryl/hetaryl chloroacetamides and benzyl chloride to produce the series of S-alkyl derivatives. The results of molecular docking studies for the obtained series of S-alkyl benzimidazole-thienopyrimidines showed their high affinity to the TrmD isolated from the P. aeruginosa. The results of antimicrobial activity screening revealed the antimicrobial properties for all of the studied molecules against both Gram-positive and Gram-negative bacteria and the Candida albicans fungal strain. The highest antimicrobial activity was determined for 2-{[6-(1H-benzimidazol-2-yl)-3,5-dimethyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-2-yl]thio}-N-(4-isopropylphenyl)acetamide, which also had the highest affinity to the TrmD inhibitor’s binding site according to the docking studies results.

Oxazolone–1,2,3-Triazole Hybrids: Design, Synthesis and Antimicrobial Evaluation

2018 ◽  
Vol 18 (17) ◽  
pp. 1506-1513 ◽  
Author(s):  
Kashmiri Lal ◽  
Lokesh Kumar ◽  
Ashwani Kumar ◽  
Anil Kumar
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Properties ◽  
Dilution Method ◽  
Antimicrobial Drugs ◽  
Activity Data ◽  
Design Synthesis ◽  
Docking Simulations ◽  
Comparable Activity ◽  
Antimicrobial Evaluation

Background: Oxazolones and 1,2,3-triazoles are among the extensively studied heterocycles in medicinal chemistry. Both of these moieties are reported to possess a broad spectrum of biological activity including antimicrobial. Objective: The objective of the current work is to design, synthesize and antimicrobial evaluation of some new oxazolone-1,2,3-triazole hybrids. Methods: The designed oxazolone-1,2,3-triazole hybrids were synthesized using copper(I)-catalyzed azide-alkyne cycloaddition. The antimicrobial evaluation was carried out using serial dilution method. Results: Most of the synthesized hybrids showed significant antimicrobial properties. Some of the compounds were found to be possessing better or comparable activity to that of the standards used. The docking simulations results are also in agreement with the antimicrobial activity data. Conclusion: Sixteen new hybrids were synthesized and tested in vitro for their antimicrobial activity. Some of the tested compounds exhibited promising antimicrobial activity and could be utilized for the development of the lead compounds for new and more potent antimicrobial drugs.

New Caffeic Acid Derivatives as Antimicrobial Agents: Design, Synthesis, Evaluation and Docking

2019 ◽  
Vol 19 (4) ◽  
pp. 292-304 ◽  
Author(s):  
Maia Merlani ◽  
Vakhtang Barbakadze ◽  
Lela Amiranashvili ◽  
Lali Gogilashvili ◽  
Vladimir Poroikov ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Caffeic Acid ◽  
Antimicrobial Agents ◽  
Biological Activities ◽  
Antimicrobial Properties ◽  
Synthesis Methods ◽  
Design Synthesis ◽  
Caffeic Acid Derivatives ◽  
Microdilution Method

Background: Phenolic acids (caffeic-, ferulic and p-coumaric acid) are widely distributed in the plant kingdom and exhibit broad spectrum of biological activities, including antimicrobial activity. Objective: The goal of this paper is the synthesis of some caffeic acid derivatives selected based on computer-aided predictions and evaluate their in vitro antimicrobial properties against Gram positive and Gram negative bacteria and also a series of fungi. Methods: In silico prediction of biological activity was used to identify the most promising structures for synthesis and biological testing, and the putative mechanisms of their antimicrobial action. The designed compounds were synthesized using classical organic synthesis methods. The antimicrobial activity was studied using microdilution method. Results: Twelve tested compounds have shown good antibacterial activity. Five out of twelve tested compounds appeared to be more active than the reference drugs ampicillin and streptomycin. Despite that all compounds exhibited good activity against all bacteria tested, the sensitivity of bacteria towards compounds in general was different. The evaluation of antifungal activity revealed that all compounds were more active than ketoconazole, while seven compounds (2, 3, 4, 5, 7, 8 and 12) appeared to be more active than bifonazole. Docking results indicate that gyrase inhibition is the putative mechanism of antibacterial action while the inhibition of 14α-demethylase may be responsible for antifungal action. Prediction of cytotoxicity by PROTOX showed that compounds are not toxic (LD50 1000-2000 mg/kg). Conclusion: Thirteen compounds, from which six are new ones, were synthesized, and twelve compounds were tested for antimicrobial activity. The studied compounds appeared to be promising potent and non-toxic antimicrobials, which could be considered as leads for new pharmaceutical agents.

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.

Synthesis, structure, photophysical, electrochemical properties and antibacterial activity of brominated BODIPYs as an inhibitor of DNA gyrase B of S. aureus

2019 ◽  
Vol 23 (06) ◽  
pp. 645-654
Author(s):  
Dijo Prasannan ◽  
Chennakkandathil Sareena ◽  
Chellaiah Arunkumar ◽  
Suchithra Tharamel Vasu
Keyword(s):  
Morphological Analysis ◽  
Antibacterial Effect ◽  
Antimicrobial Properties ◽  
Dna Gyrase ◽  
Docking Studies ◽  
Antibacterial Drug ◽  
Bacterial Cells ◽  
Mechanistic Investigation ◽  
Meso Position

BODIPYs with 3-thienyl and 4-acetamido phenyl groups substituted at the meso-position are subjected to regioselective bromination using three equivalents of [Formula: see text]-bromosuccinimide (NBS) to yield their 2-mono and 2,6-di bromoderivatives. Their photophysical, electrochemical and antimicrobial properties are investigated. This paper presents a mechanistic investigation of the antibacterial effect of brominated BODIPYs, particularly against Staphylococcus aureus. Fluorescence microscopic images reveal that the compounds are internalized effectively within the bacterial cells, making it an ideal antibacterial drug. Morphological analysis of the bacterial cells after the treatment with the test compounds showed that the compounds did not affect the cell membrane or cell wall and the antibacterial effect of these compounds is achieved via a different mechanism. The most effective compound was selected to explore the target of action. Molecular docking studies were performed on 22 selected proteins in S. aureus and the in silico results were validated by in vitro experiments. It was observed that the supercoiling activity of DNA gyrase was completely inhibited by the 2,6-dibromo-1,3,5,7-tetramethyl-8-(4-acetamido)-4-bora-3a,4a-diaza-[Formula: see text]-indacene, 3c by forming H-bonds with the ASP 81 residue of the enzyme.

scholarly journals DESIGN, SYNTHESIS, AND PHARMACOLOGICAL EVALUATION OF SOME NOVEL BIS-THIAZOLE DERIVATIVES

2018 ◽  
Vol 11 (4) ◽  
pp. 164 ◽  
Author(s):  
Ramesh M Borde ◽  
Satish B Jadhav ◽  
Rahul R Dhavse ◽  
Achut S Munde
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Properties ◽  
Hantzsch Reaction ◽  
Thiazole Derivatives ◽  
Design Synthesis ◽  
Structure Activity ◽  
Elemental Analyses ◽  
And Staphylococcus Aureus ◽  
Toxic Molecule

 Objective: A series of substituted 5,2-bis-thiazoles derivatives were synthesized by Hantzsch reaction and evaluated in vitro for antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Staphylococcus aureus. Methods: 2-(4-(benzyloxy)phenyl)-4-methylthiazole-5-carbothioamide were synthesized and allowed to react with various α-haloketones to give 5,2-bis-thiazoles, i.e., 2-(4-(benzyloxy)phenyl)-4-methyl-5-(4-substituted thiazol-2-yl)thiazole derivatives in excellent yield. The synthesized compounds were characterized by spectroscopic methods as well as elemental analyses. They were screened for their antimicrobial activity using the agar diffusion method.Result: Literature survey reveals that the synthesis of 2-(4-(benzyloxy)phenyl)-4-methyl-5-(4-substituted thiazol-2-yl)thiazole, i.e., (5,2-Bis-thiazoles) derivatives (10a-e) was not reported. The entire compound exhibited mild to moderate antimicrobial activity.Conclusion: The antimicrobial results revealed that the synthesized derivatives have significant antimicrobial properties, and further, structure– activity relationship studies may develop more potent and less toxic molecule.

scholarly journals Antimicrobial activity of a novel Spanish propolis against planktonic and sessile oral Streptococcus spp

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
M. Luisa Navarro-Pérez ◽  
Virginia Vadillo-Rodríguez ◽  
Irene Fernández-Babiano ◽  
Ciro Pérez-Giraldo ◽  
M. Coronada Fernández-Calderón
Keyword(s):  
Antimicrobial Activity ◽  
Biofilm Formation ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Antimicrobial Properties ◽  
Ethanolic Extract ◽  
Oral Streptococcus ◽  
Ancient Times ◽  
Ethanolic Extract Of Propolis

AbstractIncreased bacterial resistance to traditional antimicrobial agents has prompted the use of natural products with antimicrobial properties such as propolis, extensively employed since ancient times. However, the chemical composition of propolis extracts is extremely complex and has been shown to vary depending on the region and season of collection, due to variations in the flora from which the pharmacological substances are obtained, being therefore essential for their antimicrobial activity to be checked before use. For this purpose, we evaluate the in vitro antimicrobial and anti-biofilm activity of a new and promising Spanish ethanolic extract of propolis (SEEP) on Streptococcus mutans and Streptococcus sanguinis, responsible, as dominant ‘pioneer’ species, for dental plaque. Results reveal that S. sanguinis is more sensitive to SEEP, slowing and retarding its growth considerably with lower concentrations than those needed to produce the same effect in S. mutans. SEEP presents concentration- and time-dependent killing activity and, furthermore, some of the subinhibitory concentrations employed increased biofilm formation even when bacterial growth decreased. Mono and dual-species biofilms were also inhibited by SEEP. Findings obtained clearly show the relevance of using biofilm and subinhibitory concentration models to determine optimal treatment concentrations.

scholarly journals Synthesis, Spectral Analysis, In Vitro Microbiological Evaluation, and Molecular Docking Studies of Some Novel 1-(1-Aryl-1H-tetrazol-5-yl)-2-(piperidin-1-yl)ethanone Derivatives

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Thangasamy Elavarasan ◽  
Durairaj Peter Bhakiaraj ◽  
Mannathusamy Gopalakrishnan
Keyword(s):  
Antimicrobial Activity ◽  
Docking Studies ◽  
Dilution Method ◽  
Reference Drug ◽  
Mass Spectral ◽  
Drug Candidates ◽  
H Nmr ◽  
Serial Dilution Method ◽  
C Nmr

A new series of novel heterocyclic compounds containing both tetrazoles and piperidine nuclei together, namely, 1-(1-aryl-1H-tetrazol-5-yl)-2-(piperidin-1-yl)ethanone (22–28), were synthesized by the treatment of the respective 2-chloro-1-(1-aryl-1H-tetrazol-5-yl)ethanone (15–21) with piperidine in acetonitrile for 6 h. A series of novel tetrazole substituted piperidine derivatives were synthesized and evaluated for their antimicrobial activity using serial dilution method. The structures of the synthesized compounds were characterized by IR, 1H NMR, 13C NMR, mass spectral data, and elemental analysis. Evaluation of antimicrobial activity shows that several compounds exhibit good activity when compared with the reference drug candidates and thus could be promising new lead molecules.

Design, Synthesis and Docking Studies of Some Novel Fluoroquinolone Compounds with Antibacterial Activity

2018 ◽  
Vol 69 (4) ◽  
pp. 815-822 ◽  
Author(s):  
Lucia Pintilie ◽  
Amalia Stefaniu ◽  
Alina Ioana Nicu ◽  
Maria Maganu ◽  
Miron Teodor Caproiu
Keyword(s):  
Antimicrobial Activity ◽  
Antibacterial Activity ◽  
Molecular Docking ◽  
Drug Discovery ◽  
Elemental Analysis ◽  
Docking Studies ◽  
Receptor Protein ◽  
Chemical Methods ◽  
Design Synthesis ◽  
Gram Negative

A new series of fluoroquinolone compounds have been obtained by Gould-Jacobs method. The compounds have been characterized by physic-chemical methods (elemental analysis, FTIR, NMR, UV-Vis) and by antimicrobial activity against Gram-positive and Gram-negative microorganisms. For the synthesized compounds have been performed calculations of characteristics and molecular properties, using Spartan�14 Software from Wavefunction, Inc. Irvine, CA. and molecular docking studies using CLC Drug Discovery Workbench 2.4 software, to identify and visualize the most likely interaction ligand (fluoroquinolone) with the receptor protein.

Design, Synthesis and Pharmacological Evaluation of Novel Antiinflammatory and Analgesic O-Benzyloxime Compounds Derived From Natural Eugenol

2019 ◽  
Vol 16 (10) ◽  
pp. 1157-1166
Author(s):  
Rodrigo César da Silva ◽  
Fabiano Veiga ◽  
Fabiana Cardoso Vilela ◽  
André Victor Pereira ◽  
Thayssa Tavares da Silva Cunha ◽  
...  
Keyword(s):  
Formalin Test ◽  
Docking Studies ◽  
Paw Edema ◽  
Inhibitory Effects ◽  
Structural Pattern ◽  
Design Synthesis ◽  
Drug Candidates ◽  
Anti Inflammatory ◽  
Analgesic Activities ◽  
Cox 1

Background: : A new series of O-benzyloximes derived from eugenol was synthesized and was evaluated for its antinociceptive and anti-inflammatory properties. Methods: : The target compounds were obtained in good global 25-28% yields over 6 steps, which led us to identify compounds (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-(4- (methylthio)benzyloxime (8b), (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-4- bromobenzyloxime (8d) and (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-4- (methylsulfonyl)benzyloxime (8f) as promising bioactive prototypes. Results:: These compounds have significant analgesic and anti-inflammatory effects, as evidenced by formalin-induced mice paw edema and carrageenan-induced mice paw edema tests. In the formalin test, compounds 8b and 8f evidenced both anti-inflammatory and direct analgesic activities and in the carrageenan-induced paw edema, with compounds 8c, 8d, and 8f showing the best inhibitory effects, exceeding the standard drugs indomethacin and celecoxib. Conclusion: : Molecular docking studies have provided additional evidence that the pharmacological profile of these compounds may be related to inhibition of COX enzymes, with slight preference for COX-1. These results led us to identify the new O-benzyloxime ethers 8b, 8d and 8f as orally bioactive prototypes, with a novel structural pattern capable of being explored in further studies aiming at their optimization and development as drug candidates.

scholarly journals Novel Derivatives of 4-Methyl-1,2,3-Thiadiazole-5-Carboxylic Acid Hydrazide: Synthesis, Lipophilicity, and In Vitro Antimicrobial Activity Screening

2021 ◽  
Vol 11 (3) ◽  
pp. 1180
Author(s):  
Kinga Paruch ◽  
Łukasz Popiołek ◽  
Anna Biernasiuk ◽  
Anna Berecka-Rycerz ◽  
Anna Malm ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Carboxylic Acid ◽  
Bacterial Infections ◽  
Acid Hydrazide ◽  
Antimicrobial Effect ◽  
In Vitro Antimicrobial Activity ◽  
Research Goal ◽  
New Compounds ◽  
Derivatives Of

Bacterial infections, especially those caused by strains resistant to commonly used antibiotics and chemotherapeutics, are still a current threat to public health. Therefore, the search for new molecules with potential antimicrobial activity is an important research goal. In this article, we present the synthesis and evaluation of the in vitro antimicrobial activity of a series of 15 new derivatives of 4-methyl-1,2,3-thiadiazole-5-carboxylic acid. The potential antimicrobial effect of the new compounds was observed mainly against Gram-positive bacteria. Compound 15, with the 5-nitro-2-furoyl moiety, showed the highest bioactivity: minimum inhibitory concentration (MIC) = 1.95–15.62 µg/mL and minimum bactericidal concentration (MBC)/MIC = 1–4 µg/mL.

Sign in / Sign up

Export Citation Format

Share Document