scholarly journals Synthesis, Identification, Computer-Aided Docking Studies, and ADMET Prediction of Novel Benzimidazo-1,2,3-triazole Based Molecules as Potential Antimicrobial Agents

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7119
Author(s):  
Huda R. M. Rashdan ◽  
Aboubakr H. Abdelmonsef ◽  
Mortaga M. Abou-Krisha ◽  
Tarek A. Yousef
Keyword(s):  
Antimicrobial Activity ◽  
Binding Energy ◽  
Antimicrobial Agents ◽  
Sodium Ethoxide ◽  
Dna Gyrase ◽  
Docking Studies ◽  
Bacterial Strains ◽  
Standard Drug ◽  
E Coli

2-azido-1H-benzo[d]imidazole derivatives 1a,b were reacted with a β-ketoester such as acetylacetone in the presence of sodium ethoxide to obtain the desired molecules 2a,b. The latter acted as a key molecule for the synthesis of new carbazone derivatives 4a,b that were submitted to react with 2-oxo-N-phenyl-2-(phenylamino)acetohydrazonoyl chloride to obtain the target thiadiazole derivatives 6a,b. The structures of the newly synthesized compounds were inferred from correct spectral and microanalytical data. Moreover, the newly prepared compounds were subjected to molecular docking studies with DNA gyrase B and exhibited binding energy that extended from −9.8 to −6.4 kcal/mol, which confirmed their excellent potency. The compounds 6a,b were found to be with the minimum binding energy (−9.7 and −9.8 kcal/mol) as compared to the standard drug ciprofloxacin (−7.4 kcal/mol) against the target enzyme DNA gyrase B. In addition, the newly synthesized compounds were also examined and screened for their in vitro antimicrobial activity against pathogenic microorganisms Staphylococcus aureus, E. coli, Pseudomonas aeruginosa, Aspergillus niger, and Candida albicans. Among the newly synthesized molecules, significant antimicrobial activity against all the tested microorganisms was obtained for the compounds 6a,b. The in silico and in vitro findings showed that compounds 6a,b were the most active against bacterial strains, and could serve as potential antimicrobial agents.

SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION OF 3-FORMYL INDOLE BASED SCHIFF BASES

2018 ◽  
Vol 7 (6) ◽  
Author(s):  
Singh Gurvinder ◽  
Singh Prabhsimran ◽  
Dhawan R. K.
Keyword(s):  
Antimicrobial Activity ◽  
Spectral Analysis ◽  
Schiff Bases ◽  
Antimicrobial Agents ◽  
Biological Evaluation ◽  
Fungal Strain ◽  
Bacterial Strains ◽  
Standard Drug ◽  
Gram Negative ◽  
E Coli

In order to develop new antimicrobial agents, a series of 3-formyl indole based Schiff bases were synthesized by reacting 3-formyl indole(indole-3-carboxaldehyde) with substituted aniline taking ethanol as solvent. The reaction was carried in the presence of small amount of p-toluene sulphonic acid as catalyst.All the synthesized compounds were characterized by IR, 1H-NMR spectral analysis. All the synthesized compounds were evaluated for antimicrobial activity against two gram positive bacterial strains (B. subtilisand S. aureus) and two gram negative bacterial strains (P. aeruginosaand E. coli) and one fungal strain (C. albicans). All the synthesized compounds were found to have moderate to good antimicrobial activity. The  standard drug amoxicillin, fluconazole were used for antimicrobial activity. Among the synthesized compounds, the maximum antimicrobial activity was shown by compounds GS04, GS07, GS08 and GS10.

Synthesis, Antimicrobial Evaluation and In silico Studies of Novel 2,4- disubstituted-1,3-thiazole Derivatives

2018 ◽  
Vol 16 (2) ◽  
pp. 160-173 ◽  
Author(s):  
Mir Mohammad Masood ◽  
Mohammad Irfan ◽  
Shadab Alam ◽  
Phool Hasan ◽  
Aarfa Queen ◽  
...  
Keyword(s):  
In Silico ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Docking Studies ◽  
Bacterial Strains ◽  
Thiazole Derivatives ◽  
Standard Drug ◽  
Hek 293 ◽  
In Silico Studies

Background: 2,4-disubstituted-1,3-thiazole derivatives (2a–j), (3a–f) and (4a–f) were synthesized, characterized and screened for their potential as antimicrobial agents. In the preliminary screening against a panel of bacterial strains, nine compounds showed moderate to potent antibacterial activity (IC50 = 13.7-90.8 μg/ml). </P><P> Methods: In the antifungal screening, compound (4c) displayed potent antifungal activity (IC50 = 26.5 &#181;g/ml) against Candida tropicalis comparable to the standard drug, fluconazole (IC50 = 10.5 &#181;g/ml). Based on in vitro antimicrobial results, compounds 2f, 4c and 4e were selected for further pharmacological investigations. Hemolytic activity using human red blood cells (hRBCs) and cytotoxicity by MTT assay on human embryonic kidney (HEK-293) cells revealed non-toxic nature of the selected compounds (2f, 4c and 4e). To ascertain their possible mode of action, docking studies with the lead inhibitors (2f, 4c and 4e) were performed using crystal structure coordinates of bacterial methionine aminopeptidases (MetAPs), an enzyme involved in bacterial protein synthesis and maturation. Results: The results of in vitro and in silico studies provide a rationale for selected compounds (2f, 4c and 4e) to be carried forward for further structural modifications and structure-activity relationship (SAR) studies against these bacterial infections. Conclusion: The study suggested binding with one or more key amino acid residues in the active site of Streptococcus pneumoniae MetAP (SpMetAP) and Escherichia coli MetAP (EcMetAP). In silico physicochemical properties using QikProp confirmed their drug likeliness.

scholarly journals Synthesis and Evaluation of Some Novel Chromone Based Dithiazoles as Antimicrobial Agents

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Naureen Aggarwal ◽  
Vishal Sharma ◽  
Harpreet Kaur ◽  
Mohan Paul Singh Ishar
Keyword(s):  
Antimicrobial Activity ◽  
Elemental Analysis ◽  
Antimicrobial Agents ◽  
Fungal Strain ◽  
Bacterial Strains ◽  
Standard Drug ◽  
Fungal Strains ◽  
Inhibitory Potential ◽  
C Nmr

Novel substituted 1,2,4-dithiazolylchromones 3a–j were synthesized by the reaction of 3-formylchromones (1a–j) with two equivalents of p-chlorothiobenzamide (2) in dry xylene and characterized spectroscopically (IR, 1H and 13C NMR, mass) and elemental analysis. All synthesized compounds were screened for in vitro antimicrobial activity against various pathogenic bacterial and fungal strains and were found to possess good to moderate inhibitory potential against all tested strains. Antimicrobial results reveal that compounds bearing lipophilic electron withdrawing groups such as chloro and bromo displayed significant inhibitory potential against both bacterial and fungal strains. Particularly, compound 3c displayed significant inhibitory against bacterial strains and compound 3h exhibits significant inhibitory potential in comparison to standard drug fluconazole against fungal strain S. cerevisiae.

scholarly journals Synthesis, Docking Studies, and In Vitro Evaluation of Some Novel Thienopyridines and Fused Thienopyridine–Quinolines as Antibacterial Agents and DNA Gyrase Inhibitors

Molecules ◽  
2019 ◽  
Vol 24 (20) ◽  
pp. 3650 ◽  
Author(s):  
Eman M. Mohi El-Deen ◽  
Eman A. Abd El-Meguid ◽  
Sherifa Hasabelnaby ◽  
Eman A. Karam ◽  
Eman S. Nossier
Keyword(s):  
Staphylococcus Aureus ◽  
Dna Gyrase ◽  
Docking Studies ◽  
Inhibition Activity ◽  
Bacterial Strains ◽  
Reference Drug ◽  
E Coli ◽  
Ic50 Values ◽  
Gyrase Inhibitors

A series of novel thienopyridines and pyridothienoquinolines (3a,b–14) was synthesized, starting with 2-thioxo-1,2-dihydropyridine-3-carbonitriles 1a and 1b. All compounds were evaluated for their in vitro antimicrobial activity against six bacterial strains. Compounds 3a,b, 4a, 5b, 6a,b, 7a, 9b, 12b, and 14 showed significant growth inhibition activity against both Gram-positive and Gram-negative bacteria compared with the reference drug. The most active compounds (4a, 7a, 9b, and 12b) against Staphylococcus aureus were also tested for their in vitro inhibitory action on methicillin-resistant Staphylococcus aureus (MRSA). The tested compounds showed promising inhibition activity, with the performance of 12b being equal to gentamicin and that of 7a exceeding it. Moreover, the most promising compounds were also screened for their Escherichia coli DNA gyrase inhibitory activity, compared with novobiocin as a reference DNA gyrase inhibitor. The results revealed that compounds (3a, 3b, 4a, 9b, and 12b) had the highest inhibitory capacity, with IC50 values of 2.26–5.87 µM (that of novobiocin is equal to 4.17 µM). Docking studies were performed to identify the mode of binding of the tested compounds to the active site of E. coli DNA gyrase B.

Experimental and theoretical investigation of new 1,3,4-oxadiazole based dioxovanadium (VO+2) complexes and their in-vitro antimicrobial potency

2021 ◽  
Vol 11 (6) ◽  
pp. 888-903
Author(s):  
Hanan Alghamdi ◽  
Syed Nazreen ◽  
Ahmed A. Elhenawy ◽  
Mohamed Abdelbaset
Keyword(s):  
Thermal Analysis ◽  
Antimicrobial Activity ◽  
Biological System ◽  
Antimicrobial Agents ◽  
Dna Gyrase ◽  
Fungal Strain ◽  
Interaction Mode ◽  
Vanadium Ions ◽  
Antimicrobial Potency

The antimicrobial resistance is a global human threat which has led to the withdrawal of antibiotics from the market. Therefore, it is a need to develop new and effective antimicrobial agents to overcome this problem. In this paper, new Dioxovanadium(V) complexes (1–8) with ligands viz. (2-(5-phenyl-1,3,4-oxadiazole-2-yl)phenol; L1) and 2,5-bis(2-hydroxyphenyl)-1,3,4-oxadiazole (L2) were synthesized and assessed for antimicrobial-activity. Both a bidentate and tetradentate oxadiazole ligands coordinate with vanadium ions through the nitrogen and oxygen atoms giving octahedral geometries. Thermal analysis and IR data confirmed the presence of hydrated water in the metal-complexes. The investigated compounds were assessed for antimicrobial viz four strains of bacterial and one a fungal strain. The antibacterial data showed that, the complexes (1–8) are lower potency against bacterial strain than the free ligands except (5) and (7) complexes. These complexness showed the highest antibacterial potency via the Staphylococcus aureus. All investigated compounds were inactive against C. albicans except complexes 2 and 5 which showed high activity. The performance of DFT was conducted to examine an interaction mode of the target compounds with biological system. The QSPR was calculated as: optimization geometries, (FMOs), and chemical-reactivities for the synthesized compounds. The (MEPs) were figured to predict the interaction behavior of the ligand and its complexes against the receptor. The molecular docking was performed against DNA gyrase to study the interaction mode with biological system.

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.

scholarly journals Synthesis of sulfonamides bearing 1,3,5-triarylpyrazoline and 4-thiazolidinone moieties as novel antimicrobial agents

2020 ◽  
Vol 85 (2) ◽  
pp. 155-162
Author(s):  
Thi-Dan Thach ◽  
Thi Le ◽  
Thien-Annguyen Nguyen ◽  
Chi-Hien Dang ◽  
Van-Su Dang ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Antimicrobial Activities ◽  
Significant Inhibition ◽  
Mercaptoacetic Acid ◽  
Bacterial Strains ◽  
Reference Drug ◽  
E Coli ◽  
Yeast Strains ◽  
Microbial Strains

Two series of sulfonamides were synthesized from 4-hydrazinylbenzenesulfonamide as the key starting material. 1,3,5-Triarylpyrazoline sulfonamides (2a?i) were obtained by cyclocondensation of various chalcones in 53? ?64 % yields, while 4-thiazolidinone derivatives (4a?e) were synthesized by cyclocondensation between mercaptoacetic acid and different phenylhydrazones in 43?62 % yields. The synthesized compounds were characterized based on FTIR, 1H-NMR, 13C-NMR and HRMS data. The sulfonamides were evaluated for their in vitro antimicrobial activities against four bacterial strains (E. coli, P. aeruginosa, B. subtillis and S aureus), two filamentous fungal strains (A. niger and F. oxysporum) and two yeast strains (C. albicans and S. cerevisiae). Seven pyrazolines, 2a?c and 2e?h, exhibited significant inhibition of different microbial strains. Among them, compound 2b displayed good antifungal activity against A. niger (MIC value at 12.5 ?g mL-1) over the reference drug.

scholarly journals Synthesis and Antimicrobial Evaluations of Sulfur Inserted Fluoro-Benzimidazoles

2021 ◽  
Vol 33 (7) ◽  
pp. 1525-1529
Author(s):  
Parmesh Kumar Dwivedi ◽  
Devdutt Chaturvedi
Keyword(s):  
Antimicrobial Agents ◽  
Bacterial Strains ◽  
Substituted Anilines ◽  
Gram Positive ◽  
Gram Negative ◽  
E Coli ◽  
New Compounds ◽  
Derivatives Of ◽  
Multiple Step

A new series of fluorinated sulfur inserted benzimidazole analogues Za-i were synthesized and characterized. The new compounds were screened for their antimicrobial and antioxidant potential. The synthesized compounds were obtained by multiple step synthesis, initiating from the synthesis of 5-(difluoromethoxy)-1H-benzimidazole-2-thiol X. The compounds Ya-i prepared by reacting differently substituted anilines with chloroacetylchloride and triethylamine in DMF. Finally, the compound X was reacted with different derivatives of 2-chloro-N-phenylacetamide resulting in formation of titled compounds Za-i. The synthesized compounds (Za-Zi) were characterized by spectral analysis viz.1H & 13C NMR, mass spectra, elemental analysis and IR. The in vitro antimicrobial potential against Gram-positive (S. aureus and E. faecalis) and Gram-negative bacterial (E. coli and P.aeruginosa) strains as well as fungi (A. niger and C. albicans) was recorded for the obtained compounds. Some of the compounds exhibited encouraging results (in MIC) against Gram-positive and Gram-negative bacterial strains. These studies thus suggest that the designed sulfur inserted fluoro-benzimidazoles scaffold may serve as new promising template for further amplification as antimicrobial agents.

Preparation of a Novel Complex Antimicrobial Agent and its Antimicrobial Activity In Vitro

2012 ◽  
Vol 550-553 ◽  
pp. 1030-1038
Author(s):  
Peng Li ◽  
Wei Guo Wang ◽  
Yu Jia Cui ◽  
Yong Liang Zhao ◽  
Ya Nan Gu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Antimicrobial Agent ◽  
Antimicrobial Agents ◽  
E Coli ◽  
Orthogonal Experiments ◽  
Novel Complex ◽  
Cefoperazone Sodium ◽  
Complex Antimicrobial Agent

Purpose To develop a novel complex antimicrobial agent and determine the optimal components of the composite antimicrobial agents and its antimicrobial activity in vitro. Methods According to antimicrobial mechanisms，antibacterial spectrums，physical and chemical properties and applicabilities of existing antimicrobial agents in clinical use, select out cefoperazone sodium, sulbactam sodium and cephradine as the basic components to make a novel complex antimicrobial agent. Utilize yeast, staphylococcus aureus and E. coli bacteria as test bacteria. Do the three factors four-level orthogonal experiments by the maximum amount, the middle amount, low amount and Minimum amount of the three-component agent to research the optimum ratio of the drug. Measure the titer of the compound antimicrobial agent by the way of tube-plate method (2 doses). With known contents of Penicillin Sodium for Injection as control, and determine its minimum inhibitory concentration against staphylococcus aureus, E. coli and yeast by using the agar doubling dilution method. The experimental results were analysized by statistical analysis software SPSS16.0. Results The results of the three factors four-level orthogonal experiments indicate the optimum ratios of Cefoperazone Sodium, Sulbactam Sodium and Cephradine against E. coli, yeast and staphylococcus aureus were 2:2:3, 1:2:2 and 2:6:5, their titers were 1353.9U/mg, 982.7U/mg and 1015.5U/mg. With the highest titer proportion 2:2:3 as the composition of the antimicrobial compound. This compound antimicrobial agent had a good antimicrobial activity against Gram-positive bacteria, Gram-negative bacteria and Fungi, its minimal inhibitory concentration (MIC) against staphylococcus aureus, E. coli and yeast were 2.000μg/ml, 0.500μg/ml and 16.000μg/ml. Conclusion This research acquires a composite of antibiotics. This antimicrobial compound has a broader spectrum and higher antimicrobial activity in vitro comparing with traditional common single antibiotics, and it especially has a good antimicrobial activity against fungi. The results set a scientific foundation for enriching clinical medicines.

New Oxadiazole Derivatives: Synthesis and Appraisal of Their Potential as Antimicrobial Agents

2018 ◽  
Vol 15 (1) ◽  
pp. 21-30
Author(s):  
Deboleena Dhara ◽  
Dhanya Sunil ◽  
Pooja R. Kamath ◽  
K. Ananda ◽  
S. Shrilakshmi ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Agents ◽  
Drug Resistant ◽  
Bacterial Strains ◽  
Spectral Techniques ◽  
Docking Simulations ◽  
E Coli ◽  
Oxadiazole Derivatives ◽  
Bacteria And Fungi ◽  
Almost All

Introduction: The escalating threat due to dwindling effect of antibiotics and challenge of tackling rising drug-resistant infections has gathered high focus in current medicinal research. Methods: In an attempt to find new molecules that can defeat microbial resistance, two new series of 2-[2-substituted ethenyl]-5-(substituted methoxy)-1,3,4-oxadiazole derivatives were synthesized. Various aromatic hydrazides were allowed to undergo cyclization to substituted oxadiazole-2- amines in the presence of cyanogen bromide and further condensed with different heterocyclic aldehydes to give new oxadiazole derivatives. The synthesized molecules were fully characterized by various spectral techniques and tested for antimicrobial activity. Results: Almost all the newly synthesized compounds especially (5g-5l) displayed remarkable growth inhibition against three bacterial strains: M. smegmatis, S. aureus, E. coli and fungi C. albicans. The antimicrobial activity was further confirmed by MIC assay against the same microorganisms. Oxadiazole 5g displayed promising activity with a MIC value of 0.025 mM for two bacteria and fungi, whereas MIC of this compound for E. coli was 0.1 mM. Other active compounds (5h-5l) also exhibited good MIC ranging between 0.313 to 5.0 mM against the selected microorganisms. Docking simulations were generated to explore the potential binding approaches of ligand 5g at the D-alanine:d-alanine ligase (Ddl) protein of E. coli and S. aureus. Conclusion: Molecule 5g was active even at a lower concentration and could probably act as a prospective lead molecule for targeting the drug resistant microorganisms.

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