Antimicrobial Evaluation, Molecular Docking and ADME Properties of Indole Amide Derivatives

2021 ◽  
Vol 18 ◽  
Author(s):  
Derya Doğanay ◽  
Sevval M. Özcan ◽  
Ahmet M. Şentürk ◽  
Süreyya Ölgen
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Antimicrobial Properties ◽  
Antimicrobial Activities ◽  
In Vitro Tests ◽  
Lipinski’S Rule ◽  
Amide Derivatives

Background: Besides the viral infections, bacterial infections can cause serious and life-threatening complications and drug resistance is an important problem to fight bacterial infections. Therefore, it is important to discover novel antimicrobial agents to fight such infections. Objective: Several indole containing antimicrobial drug development studies have been reported in literature that provided strong evidences for good antimicrobial activities against a variety of microorganisms. Taken into consideration from these findings, antimicrobial properties of previously synthesized 16 indole amide derivatives were evaluated by in vitro tests against 14 different microorganisms, and also molecular docking and in silico prediction studies were used to identify structure-activity relationship of compounds. Methods: Antimicrobial activity of compounds was determined by disc diffusion and tube dilution methods. Molecular docking of compounds was studied to determine the relationship between the structure of compounds with DNA gyrase interactions of microorganisms by using the version of Autodock vina 4.2.6. Mol inspiration and Swiss ADME prediction online software programs were also used to identify drug-like properties of compounds. Results: The results showed that some compounds exhibited quite pronounced antibacterial and antifungal activities compared to reference drugs. These results were also supported by molecular docking studies and in silico ADME calculations presented that all tested compounds obey the Lipinski’s Rule of Five and are metabolized by CYP450 enzymes. Conclusion: It can be concluded that these results can be taken as reference in the development of new indole-based antimicrobial agents.

scholarly journals Biological Evaluation and Molecular Docking with In Silico Physicochemical, Pharmacokinetic and Toxicity Prediction of Pyrazolo[1,5-a]pyrimidines

Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1431 ◽  
Author(s):  
Ahmed M. Naglah ◽  
Ahmed A. Askar ◽  
Ashraf S. Hassan ◽  
Tamer K. Khatab ◽  
Mohamed A. Al-Omar ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Biological Activities ◽  
Antimicrobial Properties ◽  
Docking Study ◽  
Biological Evaluation ◽  
Immunomodulatory Activity ◽  
Molecular Docking Study ◽  
Lipinski’S Rule

Pyrazolo[1,5-a]pyrimidines 5a–c, 9a–c and 13a–i were synthesized for evaluation of their in vitro antimicrobial properties against some microorganisms and their immunomodulatory activity. The biological activities of pyrazolo[1,5-a]pyrimidines showed that the pyrazolo[1,5-a]pyrimidines (5c, 9a, 9c, 13a, 13c, 13d, 13e and 13h) displayed promising antimicrobial and immunomodulatory activities. Studying the in silico predicted physicochemical, pharmacokinetic, ADMET and drug-likeness properties for the pyrazolo[1,5-a]pyrimidines 5a–c, 9a–c and 13a–i confirmed that most of the compounds (i) were within the range set by Lipinski’s rule of five, (ii) show higher gastrointestinal absorption and inhibition of some CYP isoforms, and (iii) have a carcinogenicity test that was predicted as negative and hERG test that presented medium risk. Moreover, the molecular docking study demonstrated that the compounds 5c, 9a, 9c, 13a, 13c, 13d, 13e and 13h are potent inhibitors of 14-alpha demethylase, transpeptidase and alkaline phosphatase enzymes. This study could be valuable in the discovery of a new series of drugs.

Synthesis, In Vitro and In Silico Studies of Indolequinone Derivatives against Clinically Relevant Bacterial Pathogens

2020 ◽  
Vol 20 (3) ◽  
pp. 192-208 ◽  
Author(s):  
Talita Odriane Custodio Leite ◽  
Juliana Silva Novais ◽  
Beatriz Lima Cosenza de Carvalho ◽  
Vitor Francisco Ferreira ◽  
Leonardo Alves Miceli ◽  
...  
Keyword(s):  
In Silico ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Mass Spectrometry Analysis ◽  
World Health ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Dione Derivative ◽  
In Silico Studies

Background: According to the World Health Organization, antimicrobial resistance is one of the most important public health threats of the 21st century. Therefore, there is an urgent need for the development of antimicrobial agents with new mechanism of action, especially those capable of evading known resistance mechanisms. Objective: We described the synthesis, in vitro antimicrobial evaluation, and in silico analysis of a series of 1H-indole-4,7-dione derivatives. Methods: The new series of 1H-indole-4,7-diones was prepared with good yield by using a copper(II)- mediated reaction between bromoquinone and β-enamino ketones bearing alkyl or phenyl groups attached to the nitrogen atom. The antimicrobial potential of indole derivatives was assessed. Molecular docking studies were also performed using AutoDock 4.2 for Windows. Characterization of all compounds was confirmed by one- and two-dimensional NMR techniques 1H and 13C NMR spectra [1H, 13C – APT, 1H x 1H – COSY, HSQC and HMBC], IR and mass spectrometry analysis. Results: Several indolequinone compounds showed effective antimicrobial profile against Grampositive (MIC = 16 µg.mL-1) and Gram-negative bacteria (MIC = 8 µg.mL-1) similar to antimicrobials current on the market. The 3-acetyl-1-(2,5-dimethylphenyl)-1H-indole-4,7-dione derivative exhibited an important effect against different biofilm stages formed by a serious hospital life-threatening resistant strain of Methicillin-Resistant Staphylococcus aureus (MRSA). A hemocompatibility profile analysis based on in vitro hemolysis assays revealed the low toxicity effects of this new series. Indeed, in silico studies showed a good pharmacokinetics and toxicological profiles for all indolequinone derivatives, reinforcing their feasibility to display a promising oral bioavailability. An elucidation of the promising indolequinone derivatives binding mode was achieved, showing interactions with important sites to biological activity of S. aureus DNA gyrase. These results highlighted 3-acetyl-1-(2-hydroxyethyl)-1Hindole- 4,7-dione derivative as broad-spectrum antimicrobial prototype to be further explored for treating bacterial infections. Conclusion: The highly substituted indolequinones were obtained in moderate to good yields. The pharmacological study indicated that these compounds should be exploited in the search for a leading substance in a project aimed at obtaining new antimicrobials effective against Gram-negative bacteria.

scholarly journals Synthesis and Antimicrobial Properties of Highly Cross-Linked pH-Sensitive Hydrogels through Gamma Radiation

Polymers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 2223
Author(s):  
Moises Bustamante-Torres ◽  
Victor H. Pino-Ramos ◽  
David Romero-Fierro ◽  
Sandra P. Hidalgo-Bonilla ◽  
Héctor Magaña ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Film Formation ◽  
Antimicrobial Properties ◽  
Ph Sensitive ◽  
Scanning Calorimetry ◽  
Polymeric Systems ◽  
E Coli ◽  
High Prevalence

The design of new polymeric systems for antimicrobial drug release focused on medical/surgical procedures is of great interest in the biomedical area due to the high prevalence of bacterial infections in patients with wounds or burns. For this reason, in this work, we present a new design of pH-sensitive hydrogels copolymerized by a graft polymerization method (gamma rays), intended for localized prophylactic release of ciprofloxacin and silver nanoparticles (AgNPs) for potential topical bacterial infections. The synthesized hydrogels were copolymerized from acrylic acid (AAc) and agar. Cross-linked hydrogel film formation depended on monomer concentrations and the degree of radiation used (Cobalt-60). The obtained hydrogel films were characterized by attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and mechanical testing. The swelling of the hydrogels was evidenced by the influence of their pH-sensitiveness. The hydrogel was loaded with antimicrobial agents (AgNPs or ciprofloxacin), and their related activity was evaluated. Finally, the antimicrobial activity of biocidal-loaded hydrogel was tested against Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) on in vitro conditions.

scholarly journals Facile Synthesis of Antimicrobial Aloe Vera-“Smart” Triiodide-PVP Biomaterials

Biomimetics ◽  
2020 ◽  
Vol 5 (3) ◽  
pp. 45 ◽  
Author(s):  
Zehra Edis ◽  
Samir Haj Bloukh
Keyword(s):  
Antimicrobial Agents ◽  
Microstructural Analysis ◽  
Aloe Vera ◽  
Antimicrobial Properties ◽  
Surgical Site Infections ◽  
Halogen Bonding ◽  
Polyglycolic Acid ◽  
Antimicrobial Activities ◽  
One Pot

Antibiotic resistance is an eminent threat for the survival of mankind. Nosocomial infections caused by multidrug resistant microorganisms are a reason for morbidity and mortality worldwide. Plant-based antimicrobial agents are based on synergistic mechanisms which prevent resistance and have been used for centuries against ailments. We suggest the use of cost-effective, eco-friendly Aloe Vera Barbadensis Miller (AV)-iodine biomaterials as a new generation of antimicrobial agents. In a facile, one-pot synthesis, we encapsulated fresh AV gel with polyvinylpyrrolidone (PVP) as a stabilizing agent and incorporated iodine moieties in the form of iodine (I2) and sodium iodide (NaI) into the polymer matrix. Ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FT-IR), x-ray diffraction (XRD), microstructural analysis by scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) verified the composition of AV-PVP-I2, AV-PVP-I2-NaI. AV, AV-PVP, AV-PVP-I2, AV-PVP-I2-NaI, and AV-PVP-NaI were tested in-vitro by disc diffusion assay and dip-coated on polyglycolic acid (PGA) sutures against ten microbial reference strains. All the tested pathogens were more susceptible towards AV-PVP-I2 due to the inclusion of “smart” triiodides with halogen bonding in vitro and on dip-coated sutures. The biocomplexes AV-PVP-I2, AV-PVP-I2-NaI showed remarkable antimicrobial properties. “Smart” biohybrids with triiodide inclusions have excellent antifungal and promising antimicrobial activities, with potential use against surgical site infections (SSI) and as disinfecting agents.

scholarly journals Synthesis, Molecular Docking and Antimicrobial Activities of 5-(4-substituted-benzyl)-2-(furan/thiophen-2-ylmethylene hydrazono)thiazolidin-4-ones

2021 ◽  
Vol 11 (4) ◽  
pp. 12434-12446
Keyword(s):  
Escherichia Coli ◽  
Molecular Docking ◽  
1H Nmr Spectroscopy ◽  
Antimicrobial Properties ◽  
Antimicrobial Activities ◽  
Docking Studies ◽  
Binding Affinities ◽  
Bacterial Strains ◽  
Effective Synthesis

In our present work, we reported an effective synthesis, molecular docking, and antimicrobial properties of novel 5-(4-substituted-benzyl)-2-(furan/thiophen-2-ylmethylene hydrazono) thiazolidin-4-ones (6a-g) and (7a-i). The structures of the synthesized compounds (6a-g) and (7a-i) were elucidated by 1H-NMR spectroscopy. The molecular docking studies were performed for all the synthesized compounds against GlcN-6P using AutoDock-tools-1.5.6 and recorded the extent of H-bonding and binding affinities. The preselected compounds via molecular docking were further tested for in vitro antimicrobial activity against five bacterial strains (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus) and two fungal strains (Candida albicans and Cryptococcus neoformans). The antimicrobial findings exhibited that the compounds possessed significant antimicrobial potential.

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.

Antimicrobial Activity of Myrtus communis L., Cinnamomum verum and Eugenia caryophyllata Alcoholic Mixtures

2020 ◽  
Vol 16 (2) ◽  
pp. 207-212
Author(s):  
Wissam Zam ◽  
Ali Ali ◽  
Walaa Ibrahim
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Antimicrobial Activities ◽  
Diffusion Method ◽  
Myrtus Communis ◽  
Myrtus Communis L ◽  
Inhibition Zones ◽  
Alcoholic Mixtures

Background and Objective: With the significant increase in the prevalence of infectious diseases and the development of drug resistance by human pathogenic bacteria, there is a continuous need to discover new antimicrobial compounds from plants. Methods: Four extracts of wild Myrtus communis L. berries (myrtle berries) were prepared with the addition of Cinnamomum verum and Eugenia caryophyllata. The extracts were screened in vitro for their antimicrobial activities using agar-well diffusion method against Escherichia coli, Staphylococcus aureus, Enterobacter cloacae, Listeria monocytogenes, Pseudomonas aeruginosa and Proteus mirabilis cultures. Results: The inhibition zones ranged from 12 to 22 mm. The MICs values of extracts lies between the ranges of 30 to 100 mg/ml. Of the extracts studied, the most active ones were those obtained from the myrtle berries:cloves, myrtle berries:cinnamon:cloves with the highest inhibition zones 22 mm and 17mm against S. aureus and L. monocytogenes at 50 mg/ml and 80 mg/ml, respectively. None of the extracts was active against E. coli and P. mirabilis. Conclusion: The present investigations have exposed that the myrtle berries:cloves, myrtle berries: cinnamon:cloves extracts could be used in traditional medicine as natural antimicrobial agents in treatment the bacterial infections.

scholarly journals Synergy of Silver Nanoparticles and Aztreonam against Pseudomonas aeruginosa PAO1 Biofilms

2014 ◽  
Vol 58 (10) ◽  
pp. 5818-5830 ◽  
Author(s):  
Marc B. Habash ◽  
Amber J. Park ◽  
Emily C. Vis ◽  
Robert J. Harris ◽  
Cezar M. Khursigara
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Silver Nanoparticles ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Cell Envelope ◽  
Antimicrobial Properties ◽  
Planktonic Cell ◽  
Chronic Infections ◽  
Content Type

ABSTRACTPathogenic bacterial biofilms, such as those found in the lungs of patients with cystic fibrosis (CF), exhibit increased antimicrobial resistance, due in part to the inherent architecture of the biofilm community. The protection provided by the biofilm limits antimicrobial dispersion and penetration and reduces the efficacy of antibiotics that normally inhibit planktonic cell growth. Thus, alternative antimicrobial strategies are required to combat persistent infections. The antimicrobial properties of silver have been known for decades, but silver and silver-containing compounds have recently seen renewed interest as antimicrobial agents for treating bacterial infections. The goal of this study was to assess the efficacy of citrate-capped silver nanoparticles (AgNPs) of various sizes, alone and in combination with the monobactam antibiotic aztreonam, to inhibitPseudomonas aeruginosaPAO1 biofilms. Among the different sizes of AgNPs examined, 10-nm nanoparticles were most effective in inhibiting the recovery ofP. aeruginosabiofilm cultures and showed synergy of inhibition when combined with sub-MIC levels of aztreonam. Visualization of biofilms treated with combinations of 10-nm AgNPs and aztreonam indicated that the synergistic bactericidal effects are likely caused by better penetration of the small AgNPs into the biofilm matrix, which enhances the deleterious effects of aztreonam against the cell envelope ofP. aeruginosawithin the biofilms. These data suggest that small AgNPs synergistically enhance the antimicrobial effects of aztreonam againstP. aeruginosain vitro, and they reveal a potential role for combinations of small AgNPs and antibiotics in treating patients with chronic infections.

In vitro antimicrobial activity of the leaf extract of Harungana madagascariensis Lam. ex Poir. (Hypericaceae) against strains causing otitis externa in dogs and cats

2007 ◽  
Vol 55 (1) ◽  
pp. 97-105 ◽  
Author(s):  
B. Moulari ◽  
Y. Pellequer ◽  
J. Chaumont ◽  
Y. Guillaume ◽  
J. Millet
Keyword(s):  
Otitis Externa ◽  
Leaf Extract ◽  
Antimicrobial Agents ◽  
Antimicrobial Properties ◽  
Antimicrobial Activities ◽  
Phytochemical Analysis ◽  
Malassezia Pachydermatis ◽  
Staphylococcus Intermedius ◽  
Phytochemical Investigation

Otitis externa in dogs and cats is always caused by a combination of yeasts and bacteria, among which the most important are Malassezia pachydermatis, Staphylococcus intermedius and Pseudomonas species. These organisms often develop resistance to classical antimicrobial agents. Therefore, the aim of this study was to investigate the antimicrobial activities of an ethyl acetate leaf extract of Harungana madagascariensis against the organisms cited, to carry out the phytochemical investigation of this extract and to determine its bioactive chemical class using dilution techniques, the bioautography method and the standard phytochemical method described by Harborne (1973). Phytochemical analysis revealed the presence of saponins, tannins, flavonoids, alkaloids and anthracenic derivatives. The bioassay showed that the antimicrobial properties may be attributed to astilbin, a flavanone derivative identified on the basis of its spectroscopic data. The results suggest that the extract could be used in an antimicrobial preparation effective against the whole range of organisms incriminated in otitis externa in dogs and cats, with a minimal inhibitory concentration (MIC) of 250 μg/ml.

Synthesis of Novel Hydrazones of Levofloxacin related molecule and their In Vitro evaluation as antioxidant, and Molecular Docking Studies

2020 ◽  
Vol 23 ◽  
Author(s):  
Bharat B. Kashid ◽  
Jaydeo T. Kilbile ◽  
Kishor D. Wani ◽  
Suhas. M. Pawar ◽  
Vijay M. Khedkar ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Interaction Analysis ◽  
Radical Scavenging Activity ◽  
Research Work ◽  
Radical Scavenging ◽  
Butylated Hydroxytoluene ◽  
Lipinski’S Rule ◽  
Antioxidant Agents

Objective: The research work aims synthesis of novel series of hydrazones, antioxidant screening, evaluate the binding affinities, and in silico methods for the identification of possible drug targets of synthesized compounds. Methods: This report briefly explains the synthesis of novel series of hydrazones was synthesized via. hydrazinolysis of esters to obtain hydrazide, treated with aldehyde and acetophenone to get hydrazones. The spectral confirmed hydrazones exhibited excellent to comparable anti-oxidant as compaired to the standard drugs Butylated hydroxytoluene (BHT) and Ascorbic acid. Molecular docking on myeloperoxidase (MPO) demonstrated the ability of this scaffold to correctly recognize the target and engage in significant bonded and non-bonded interactions with key residues therein. Results and Discussion: In this study, we report an effectively synthesized compounds BK-35, BK-41, BK-26, BK-28 and BK-39 showed the best DPPH radical scavenging activity. The docking results clearly showed the binding mode of hydrazones into the active site of Myeloperoxidase (MPO). An in-silico results, no any of the synthesized compounds BK24 to BK-41 violated Lipinski’s rule of five (miLog P ≤ 5). Conclusions: In vitro preliminary antioxidant screening results in support by in Silico binding affinity data of novel hydrazones of levofloxacin related molecules BK-24 to BK-41 reported here have emerged as excellent antioxidant agents. The inference derived from the in vitro antioxidant screening data and the quantitative insights derived from the per-residue interaction analysis with MPO enzyme, are now being fruitfully utilized for site specific mutation around the nucleus to identify selective and potent antioxidants.

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