Antimicrobial Screening, in Silico Studies and QSAR of Chalcone-based 1,4-disubstituted 1,2,3-triazole Hybrids

Drug Research ◽  
2020 ◽  
Author(s):  
Pinki Yadav ◽  
Kashmiri Lal ◽  
Ashwani Kumar
Keyword(s):  
Topoisomerase Ii ◽  
Antimicrobial Properties ◽  
Qsar Model ◽  
Quantitative Structure Activity Relationship ◽  
Binding Modes ◽  
E Coli ◽  
Structure Activity ◽  
In Silico Studies ◽  
Microbial Strains

AbstractThe in vitro antimicrobial properties of some chalcones (1a–1c ) and chalcone tethred 1,4-disubstituted 1,2,3-triazoles (2a–2u) towards different microbial strains viz. Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Aspergillus niger and Candida albicans are reported. Compounds 2g and 2u exhibited better potency than the standard Fluconazole with MIC values of 0.0063 µmol/mL and 0.0068 µmol/mL, respectively. Furthermore, molecular docking was performed to investigate the binding modes of two potent compounds 2q and 2g with E. coli topoisomerase II DNA gyrase B and C. albicans lanosterol 14α-demethylase, respectively. Based on these results, a statistically significant quantitative structure activity relationship (QSAR) model was successfully summarized for antibacterial activity against B. subtilis.

scholarly journals Chemical Characterization and Biological Properties of NVC-422, a Novel, StableN-Chlorotaurine Analog

2011 ◽  
Vol 55 (6) ◽  
pp. 2688-2692 ◽  
Author(s):  
Lu Wang ◽  
Barbara Belisle ◽  
Mansour Bassiri ◽  
Ping Xu ◽  
Dmitri Debabov ◽  
...  
Keyword(s):  
Antimicrobial Properties ◽  
Chemical Characterization ◽  
Biological Properties ◽  
Microbial Pathogens ◽  
Antibiotic Resistant ◽  
Content Type ◽  
E Coli ◽  
Gram Positive Bacteria ◽  
Microbial Strains

ABSTRACTDuring oxidative burst, neutrophils selectively generate HOCl to destroy invading microbial pathogens. Excess HOCl reacts with taurine, a semi-essential amino acid, resulting in the formation of the longer-lived biogenerated broad-spectrum antimicrobial agent,N-chlorotaurine (NCT). In the presence of an excess of HOCl or under moderately acidic conditions, NCT can be further chlorinated, or it can disproportionate to produceN,N-dichlorotaurine (NNDCT). In the present study, 2,2-dimethyltaurine was used to prepare a more stableN-chlorotaurine, namely,N,N-dichloro-2,2-dimethyltaurine (NVC-422). In addition, we report on the chemical characterization,in vitroantimicrobial properties, and cytotoxicity of this compound. NVC-422 was shown effectively to kill all 17 microbial strains tested, including antibiotic-resistantStaphylococcus aureusandEnterococcus faecium. The minimum bactericidal concentration of NVC-422 against Gram-negative and Gram-positive bacteria ranged from 0.12 to 4 μg/ml. The minimum fungicidal concentrations againstCandida albicansandCandida glabratawere 32 and 16 μg/ml, respectively. NVC-422 has anin vitrocytotoxicity (50% cytotoxicity = 1,440 μg/ml) similar to that of NNDCT. Moreover, our data showed that this agent possesses rapid, pH-dependent antimicrobial activity. At pH 4, NVC-422 completely killed bothEscherichia coliandS. aureuswithin 5 min at a concentration of 32 μg/ml. Finally, the effect of NVC-422 in the treatment of anE. coli-infected granulating wound rat model was evaluated. Treatment of the infected granulating wound with NVC-422 resulted in significant reduction of the bacterial tissue burden and faster wound healing compared to a saline-treated control. These findings suggest that NVC-422 could have potential application as a topical antimicrobial.

scholarly journals Design, Synthesis, and Evaluation of Novel 3-Carboranyl-1,8-Naphthalimide Derivatives as Potential Anticancer Agents

2021 ◽  
Vol 22 (5) ◽  
pp. 2772
Author(s):  
Sebastian Rykowski ◽  
Dorota Gurda-Woźna ◽  
Marta Orlicka-Płocka ◽  
Agnieszka Fedoruk-Wyszomirska ◽  
Małgorzata Giel-Pietraszuk ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Anticancer Agents ◽  
Topoisomerase Ii ◽  
Cancer Cell Line ◽  
Principal Component ◽  
Quantitative Structure Activity Relationship ◽  
Field Analysis ◽  
Design Synthesis ◽  
Structure Activity

We synthesized a series of novel 3-carboranyl-1,8-naphthalimide derivatives, mitonafide and pinafide analogs, using click chemistry, reductive amination and amidation reactions and investigated their in vitro effects on cytotoxicity, cell death, cell cycle, and the production of reactive oxygen species in a HepG2 cancer cell line. The analyses showed that modified naphthalic anhydrides and naphthalimides bearing ortho- or meta-carboranes exhibited diversified activity. Naphthalimides were more cytotoxic than naphthalic anhydrides, with the highest IC50 value determined for compound 9 (3.10 µM). These compounds were capable of inducing cell cycle arrest at G0/G1 or G2M phase and promoting apoptosis, autophagy or ferroptosis. The most promising conjugate 35 caused strong apoptosis and induced ROS production, which was proven by the increased level of 2′-deoxy-8-oxoguanosine in DNA. The tested conjugates were found to be weak topoisomerase II inhibitors and classical DNA intercalators. Compounds 33, 34, and 36 fluorescently stained lysosomes in HepG2 cells. Additionally, we performed a similarity-based assessment of the property profile of the conjugates using the principal component analysis. The creation of an inhibitory profile and descriptor-based plane allowed forming a structure–activity landscape. Finally, a ligand-based comparative molecular field analysis was carried out to specify the (un)favorable structural modifications (pharmacophoric pattern) that are potentially important for the quantitative structure–activity relationship modeling of the carborane–naphthalimide conjugates.

scholarly journals Quantitative structure-activity relationships to predict antibacterial effect of some benzimidazole derivatives

2008 ◽  
pp. 181-191 ◽  
Author(s):  
Sanja Podunavac-Kuzmanovic ◽  
Dijana Barna ◽  
Dragoljub Cvetkovic
Keyword(s):  
Antibacterial Activity ◽  
Qsar Model ◽  
Quantitative Structure Activity Relationship ◽  
Biologically Active ◽  
Benzimidazole Derivatives ◽  
Quantitative Structure ◽  
Structure Activity ◽  
Lipophilicity Parameter ◽  
Office Software

The antibacterial activity of some substituted benzimidazole derivatives against Gram negative bacteria Escherichia coli was investigated. The tested compounds displayed in vitro inhibitory activity and their minimum inhibitory concentrations were determined. Quantitative structure-activity relationship has been used to study the relationships between the antibacterial activity and lipophilicity parameter, logP. Lipophilicity parameters were calculated for each molecule by using CS Chem-Office Software version 7.0. Multiple linear regression was used to correlate the logP values and antibacterial activity of benzimidazole derivatives. The results are discussed on the basis of statistical data. The most acceptable QSAR model for prediction of antibacterial activity of the investigated series of benzimidazoles was developed. High agreement between experimental and predicted inhibitory values was obtained. The results of this study indicate that the lipophilicity parameter has a significant effect on antibacterial activity of this class of compounds, thus simplifying design of new biologically active molecules.

Hybrid Imidazole-Pyridine Derivatives: An Approach to Novel Anticancer DNA Intercalators

2020 ◽  
Vol 27 (1) ◽  
pp. 154-169 ◽  
Author(s):  
Claudiu N. Lungu ◽  
Bogdan Ionel Bratanovici ◽  
Maria Mirabela Grigore ◽  
Vasilichia Antoci ◽  
Ionel I. Mangalagiu
Keyword(s):  
Experimental Data ◽  
Antimicrobial Properties ◽  
Qsar Model ◽  
Therapeutic Effectiveness ◽  
Computational Results ◽  
Pyridine Derivatives ◽  
Quadruplex Dna ◽  
Dna Intercalators ◽  
Structure Activity ◽  
G Quadruplex

Lack of specificity and subsequent therapeutic effectiveness of antimicrobial and antitumoral drugs is a common difficulty in therapy. The aim of this study is to investigate, both by experimental and computational methods, the antitumoral and antimicrobial properties of a series of synthesized imidazole-pyridine derivatives. Interaction with three targets was discussed: Dickerson-Drew dodecamer (PDB id 2ADU), G-quadruplex DNA string (PDB id 2F8U) and DNA strain in complex with dioxygenase (PDB id 3S5A). Docking energies were computed and represented graphically. On them, a QSAR model was developed in order to further investigate the structure-activity relationship. Results showed that synthesized compounds have antitumoral and antimicrobial properties. Computational results agreed with the experimental data.

Biological and In silico Studies on Synthetic Analogues of Tyrosine Betaine as Inhibitors of Neprilysin - A Drug Target for the Treatment of Heart Failure

2018 ◽  
Vol 24 (17) ◽  
pp. 1899-1904
Author(s):  
Daniel Fabio Kawano ◽  
Marcelo Rodrigues de Carvalho ◽  
Mauricio Ferreira Marcondes Machado ◽  
Adriana Karaoglanovic Carmona ◽  
Gilberto Ubida Leite Braga ◽  
...  
Keyword(s):  
Heart Failure ◽  
Secondary Metabolites ◽  
Structural Similarity ◽  
Structural Features ◽  
Major Constituent ◽  
Binding Modes ◽  
Starting Point ◽  
In Silico Studies ◽  
Nep Inhibition

Background: Fungal secondary metabolites are important sources for the discovery of new pharmaceuticals, as exemplified by penicillin, lovastatin and cyclosporine. Searching for secondary metabolites of the fungi Metarhizium spp., we previously identified tyrosine betaine as a major constituent. Methods: Because of the structural similarity with other inhibitors of neprilysin (NEP), an enzyme explored for the treatment of heart failure, we devised the synthesis of tyrosine betaine and three analogues to be subjected to in vitro NEP inhibition assays and to molecular modeling studies. Results: In spite of the similar binding modes with other NEP inhibitors, these compounds only displayed moderate inhibitory activities (IC50 ranging from 170.0 to 52.9 µM). However, they enclose structural features required to hinder passive blood brain barrier permeation (BBB). Conclusions: Tyrosine betaine remains as a starting point for the development of NEP inhibitors because of the low probability of BBB permeation and, consequently, of NEP inhibition at the Central Nervous System, which is associated to an increment in the Aβ levels and, accordingly, with a higher risk for the onset of Alzheimer's disease.

scholarly journals Molecular Shape Descriptors. 2. Quantitative Structure-Activity Relationships Based Upon Three-Dimensional Molecular Shape Descriptor

1985 ◽  
Vol 40 (11) ◽  
pp. 1114-1120
Author(s):  
loan Motoc ◽  
Garland R. Marshall
Keyword(s):  
Enzyme Inhibitor ◽  
Three Dimensional ◽  
Shape Descriptor ◽  
Molecular Shape ◽  
Quantitative Structure Activity Relationship ◽  
Quantitative Structure ◽  
E Coli ◽  
Interactional Pattern ◽  
Structure Activity ◽  
Quantitative Structure Activity Relationships

A methodology to incorporate the three-dimensional molecular shape descriptor (3 D-MSD) into a quantitative structure-activity relationship is discussed in detail. The 3 D-MSD is calculated and correlated with Kiapp values for a set of 2,4-diamino-5-benzylpyrimidines which inhibit E. coli DHFR. The correlation (n = 22, r = 0.95, s = 0.214, F = 55.10) indicates that the polarization interaction dominates the enzyme-inhibitor interactional pattern.

scholarly journals Development of a new quantitative structure–activity relationship model for predicting Ames mutagenicity of food flavor chemicals using StarDrop™ auto-Modeller™

2021 ◽  
Vol 43 (1) ◽  
Author(s):  
Toshio Kasamatsu ◽  
Airi Kitazawa ◽  
Sumie Tajima ◽  
Masahiro Kaneko ◽  
Kei-ichi Sugiyama ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Ames Test ◽  
Qsar Model ◽  
Quantitative Structure Activity Relationship ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Low Molecular Weight ◽  
Quantitative Structure ◽  
Industrial Chemicals ◽  
Structure Activity

Abstract Background Food flavors are relatively low molecular weight chemicals with unique odor-related functional groups that may also be associated with mutagenicity. These chemicals are often difficult to test for mutagenicity by the Ames test because of their low production and peculiar odor. Therefore, application of the quantitative structure–activity relationship (QSAR) approach is being considered. We used the StarDrop™ Auto-Modeller™ to develop a new QSAR model. Results In the first step, we developed a new robust Ames database of 406 food flavor chemicals consisting of existing Ames flavor chemical data and newly acquired Ames test data. Ames results for some existing flavor chemicals have been revised by expert reviews. We also collected 428 Ames test datasets for industrial chemicals from other databases that are structurally similar to flavor chemicals. A total of 834 chemicals’ Ames test datasets were used to develop the new QSAR models. We repeated the development and verification of prototypes by selecting appropriate modeling methods and descriptors and developed a local QSAR model. A new QSAR model “StarDrop NIHS 834_67” showed excellent performance (sensitivity: 79.5%, specificity: 96.4%, accuracy: 94.6%) for predicting Ames mutagenicity of 406 food flavors and was better than other commercial QSAR tools. Conclusions A local QSAR model, StarDrop NIHS 834_67, was customized to predict the Ames mutagenicity of food flavor chemicals and other low molecular weight chemicals. The model can be used to assess the mutagenicity of food flavors without actual testing.

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.

Computational Atom-based Three-Dimensional Quantitative Structure-Activity Relationship (3D QSAR) Model for Predicting Anti-Dengue Agents

2021 ◽  
Vol 16 (10) ◽  
pp. 50-58
Author(s):  
Ali Qusay Khalid ◽  
Vasudeva Rao Avupati ◽  
Husniza Hussain ◽  
Tabarek Najeeb Zaidan
Keyword(s):  
Dengue Fever ◽  
Three Dimensional ◽  
3D Qsar ◽  
Qsar Model ◽  
Quantitative Structure Activity Relationship ◽  
Activity Relationship ◽  
Quantitative Structure ◽  
Contour Maps ◽  
Structure Activity ◽  
Bioactive Ligands

Dengue fever is a viral infection spread by the female mosquito Aedes aegypti. It is a virus spread by mosquitoes found all over the tropics with risk levels varying depending on rainfall, relative humidity, temperature and urbanization. There are no specific medications that can be used to treat the condition. The development of possible bioactive ligands to combat Dengue fever before it becomes a pandemic is a global priority. Few studies on building three-dimensional quantitative structure-activity relationship (3D QSAR) models for anti-dengue agents have been reported. Thus, we aimed at building a statistically validated atom-based 3D-QSAR model using bioactive ligands reported to possess significant anti-dengue properties. In this study, the Schrodinger PhaseTM atom-based 3D QSAR model was developed and was validated using known anti-dengue properties as ligand data. This model was also tested to see if there was a link between structural characteristics and anti-dengue activity of a series of 3-acyl-indole derivatives. The established 3D QSAR model has strong predictive capacity and is statistically significant [Model: R2 Training Set = 0.93, Q2 (R2 Test Set) = 0.72]. In addition, the pharmacophore characteristics essential for the reported anti-dengue properties were explored using combined effects contour maps (coloured contour maps: blue: positive potential and red: negative potential) of the model. In the pathway of anti-dengue drug development, the model could be included as a virtual screening method to predict novel hits.

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