Correlation of structural parameters with antituberculotic activity in a group of 2-benzamidobenzothiazoles

Fourteen 2-benzamidobenzothiazole derivatives substituted in the benzoyl group and 2-cinnamamidobenzothiazole have been synthesized. The prediction of active structures by the method by Topliss gives incorrect results but, as shown on the basis of the Hansch QSAR analysis, the 2-(4-dimethylaminobenzamido)benzothiazole synthesized on the basis of the QSAR procedure by Topliss behaves anomalously also in the procedure by Hansch. Regression equations of the Hansch type have been found in which the antituberculotic activity is interpreted by lipophilicity and electronic effects of substituents. When tested in vitro, the most active compounds are comparable with ethionamide.

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In vitro Cytotoxicity and Genotoxicity Analysis of Ten Tannery Chemicals Using SOS/umu Tests and High-content In vitro Micronucleus Tests

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207321666180330120248 ◽

2018 ◽

Vol 21 (4) ◽

pp. 262-270 ◽

Cited By ~ 1

Author(s):

Zehao Huang ◽

Na Li ◽

Kaifeng Rao ◽

Cuiting Liu ◽

Zijian Wang ◽

...

Keyword(s):

Micronucleus Test ◽

A549 Cells ◽

Quantitative Structure Activity Relationship ◽

In Vitro Cytotoxicity ◽

Cytotoxic Effects ◽

Qsar Analysis ◽

Cell Assays ◽

Micronucleus Tests ◽

Damaging Effects

Background: More than 2,000 chemicals have been used in the tannery industry. Although some tannery chemicals have been reported to have harmful effects on both human health and the environment, only a few have been subjected to genotoxicity and cytotoxicity evaluations. Objective: This study focused on cytotoxicity and genotoxicity of ten tannery chemicals widely used in China. Materials and Methods: DNA-damaging effects were measured using the SOS/umu test with Salmonella typhimurium TA1535/pSK1002. Chromosome-damaging and cytotoxic effects were determined with the high-content in vitro Micronucleus test (MN test) using the human-derived cell lines MGC-803 and A549. Conclusion: The cytotoxicity of the ten tannery chemicals differed somewhat between the two cell assays, with A549 cells being more sensitive than MGC-803 cells. None of the chemicals induced DNA damage before metabolism, but one was found to have DNA-damaging effects on metabolism. Four of the chemicals, DY64, SB1, DB71 and RR120, were found to have chromosome-damaging effects. A Quantitative Structure-Activity Relationship (QSAR) analysis indicated that one structural feature favouring chemical genotoxicity, Hacceptor-path3-Hacceptor, may contribute to the chromosome-damaging effects of the four MN-test-positive chemicals.

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Novel Iodinated Hydrazide-hydrazones and their Analogues as Acetyl- and Butyrylcholinesterase Inhibitors

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666200819155503 ◽

2020 ◽

Vol 20 (23) ◽

pp. 2106-2117

Author(s):

Martin Krátký ◽

Šárka Štěpánková ◽

Michaela Brablíková ◽

Katarína Svrčková ◽

Markéta Švarcová ◽

...

Keyword(s):

Biological Activities ◽

Structural Parameters ◽

Covalent Binding ◽

Docking Studies ◽

Potent Inhibition ◽

Brain Barrier Permeability ◽

Electric Eel ◽

Ic50 Values ◽

Ellman’S Method

Background: Hydrazide-hydrazones have been known as scaffold with various biological activities including inhibition of acetyl- (AChE) and butyrylcholinesterase (BuChE). Cholinesterase inhibitors are mainstays of dementias’ treatment. Objective: Twenty-five iodinated hydrazide-hydrazones and their analogues were designed as potential central AChE and BuChE inhibitors. Methods: Hydrazide-hydrazones were synthesized from 4-substituted benzohydrazides and 2-/4- hydroxy-3,5-diiodobenzaldehydes. The compounds were investigated in vitro for their potency to inhibit AChE from electric eel and BuChE from equine serum using Ellman’s method. We calculated also physicochemical and structural parameters for CNS delivery. Results: The derivatives exhibited a moderate dual inhibition with IC50 values ranging from 15.1-140.5 and 35.5 to 170.5 μmol.L-1 for AChE and BuChE, respectively. Generally, the compounds produced a balanced or more potent inhibition of AChE. N'-[(E)-(4-Hydroxy-3,5-diiodophenyl)methylidene]-4- nitrobenzohydrazide 2k and 4-fluoro-N'-(2-hydroxy-3,5-diiodobenzyl)benzohydrazide 3a were the most potent inhibitors of AChE and BuChE, respectively. Structure-activity relationships were established, and molecular docking studies confirmed interaction with enzymes. Conclusion: Many novel hydrazide-hydrazones showed lower IC50 values than rivastigmine against AChE and some of them were comparable for BuChE to this drug used for the treatment of dementia. They interact with cholinesterases via non-covalent binding into the active site. Based on the BOILEDEgg approach, the majority of the derivatives met the criteria for blood-brain-barrier permeability.

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Synthesis of New N1Arylpiperazine Substituted Xanthine Derivatives and Evaluation of their Antioxidant and Cytotoxic Effects

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190121155651 ◽

2019 ◽

Vol 19 (4) ◽

pp. 528-537 ◽

Cited By ~ 1

Author(s):

Lily Andonova ◽

Iva Valkova ◽

Dimitrina Zheleva-Dimitrova ◽

Maya Georgieva ◽

Georgi Momekov ◽

...

Keyword(s):

Antioxidant Activity ◽

Structural Parameters ◽

Leukemia Cell ◽

Quantitative Structure Activity Relationship ◽

Cytotoxic Effects ◽

Qsar Analysis ◽

Xanthine Derivatives ◽

Human T Cell ◽

Human Acute Myeloid Leukemia ◽

Dye Reduction

Background: Cancer is one of the leading causes of morbidity and mortality worldwide, with approximately 14 million new cases in 2012, with most of the clinically used drugs being ineffective. Methylxanthines have raised more interest in research on modifying their structure because of their diverse biological activity. In addition, the piperazine nucleus is one of the most important heterocycles exhibiting remarkable pharmacological activities. Methods: The structure of the obtained compounds was characterized and elucidated by IR, 1H and 13C NMR and LCMS spectral analysis. The purity of the substances was proven by corresponding melting points and elemental analysis. The antioxidant activity was evaluated by four common methods – DPPH, ABTS, FRAP and lipid peroxidation assay. The cytotoxic effects of the tested series were evaluated using the standard MTT-dye reduction assay on three tumour cell lines. Results: A series of new xanthine derivatives comprising an arylpiperazine moiety at N1 were synthesized. The cytotoxicity against human T-cell leukemia cell SKW-3, human acute myeloid leukemia HL-60 and human Bcell precursor leukemia cell REH was evaluated. The relationship between the structure and citotoxicity of the compounds was investigated by quantitative structure-activity relationship (QSAR) analysis and the important structural parameters were drawn. Conclusion: The highest antioxidant activity was demonstrated by compound 6c. The highest cytotoxic effect was observed for compound 6f. It was found that cytotoxicity against SKW-3 depends on the electron density distribution in the structures. Branching of the molecular skeleton and introduction of heteroatoms like fluorine and sulfur in the structures also significantly improved the antiproliferative activity of the compounds.

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In silico and in vitro Study on the Inhibition of FtsZ Protein of Staphylococcus aureus by Active Compounds from Andrographis paniculata

Journal of Biologically Active Products from Nature ◽

10.1080/22311866.2021.1908163 ◽

2021 ◽

Vol 11 (2) ◽

pp. 116-128

Author(s):

Jayaraman Selvaraj ◽

Veeraraghavan Vishnu Priya ◽

Periyasamy Vijayalakshmi ◽

Rajagopal Ponnulakshmi

Keyword(s):

Staphylococcus Aureus ◽

In Silico ◽

In Vitro Study ◽

Andrographis Paniculata ◽

Vitro Study ◽

Active Compounds ◽

Ftsz Protein

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An Electrochemical Evaluation of Novel Ferrocene Derivatives for Glutamate and Liver Biomarker Biosensing

Biosensors ◽

10.3390/bios11080254 ◽

2021 ◽

Vol 11 (8) ◽

pp. 254

Author(s):

Geok Hong Soon ◽

Mary Deasy ◽

Eithne Dempsey

Keyword(s):

Film Studies ◽

Redox Potentials ◽

Signal Loss ◽

Electronic Effects ◽

Ferrocene Derivatives ◽

Electroactive Films ◽

Glutamate Oxidase ◽

Electronic Effects Of Substituents ◽

Glutamyl Transpeptidase

Here, we present an evaluation of two new monosubstituted ferrocene (Fc) derivatives, 3-(1H-pyrrol-1-yl)propanamidoferrocene and 1-hydroxy-2-[2-(thiophen-3-yl)-ethylamino]ethylferrocene, as glutamate oxidase mediators, together with their preparation and characterisation. Taking into consideration the influence of the electronic effects of substituents on the redox potentials of the Fc species, two candidates with pyrrole or thiophene moieties were proposed for investigation. Film studies involved potential sweeping in the presence of pyrrole or 3,4-ethylenedioxythiophene monomers resulting in stable electroactive films with % signal loss upon cycling ranging from 1 to 7.82% and surface coverage (Γ) 0.47–1.15 × 10−9 mol/cm2 for films formed under optimal conditions. Construction of a glutamate oxidase modified electrode resulted in second-generation biosensing with the aid of both cyclic voltammetry and hydrodynamic amperometry, resulting in glutamate sensitivity of 0.86–1.28 μA/mM and Km (app) values over the range 3.67–5.01 mM. A follow-up enzyme assay for liver biomarker γ-glutamyl transpeptidase realised unmediated and mediated measurement establishing reaction and incubation time investigations and a realising response over <100 U/L γ-glutamyl transpeptidase with a sensitivity of 5 nA/UL−1.

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Enhancement of Antioxidant and Hydrophobic Properties of Alginate via Aromatic Derivatization: Preparation, Characterization, and Evaluation

Polymers ◽

10.3390/polym13152575 ◽

2021 ◽

Vol 13 (15) ◽

pp. 2575

Author(s):

Smaher M. Elbayomi ◽

Haili Wang ◽

Tamer M. Tamer ◽

Yezi You

Keyword(s):

Radical Scavenging Activity ◽

Radical Scavenging ◽

Hydroxyl Group ◽

Hydroxyl Groups ◽

Gravimetric Analysis ◽

Scanning Calorimetry ◽

Benzoyl Group ◽

Antioxidant Evaluation ◽

Thermo Stability

The preparation of bioactive polymeric molecules requires the attention of scientists as it has a potential function in biomedical applications. In the current study, functional substitution of alginate with a benzoyl group was prepared via coupling its hydroxyl group with benzoyl chloride. Fourier transform infrared spectroscopy indicated the characteristic peaks of aromatic C=C in alginate derivative at 1431 cm−1. HNMR analysis demonstrated the aromatic protons at 7.5 ppm assigned to benzoyl groups attached to alginate hydroxyl groups. Wetting analysis showed a decrease in hydrophilicity in the new alginate derivative. Differential scanning calorimetry and thermal gravimetric analysis showed that the designed aromatic alginate derivative demonstrated higher thermo-stability than alginates. The aromatic alginate derivative displayed high anti-inflammatory properties compared to alginate. Finally, the in vitro antioxidant evaluation of the aromatic alginate derivative showed a significant increase in free radical scavenging activity compared to neat alginate against DPPH (2,2-diphenyll-picrylhydrazyl) and ABTS free radicals. The obtained results proposed that the new alginate derivative could be employed for gene and drug delivery applications.

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Design, Synthesis and Biological Evaluation of Novel Benzothiazole Based [1,2,4]Triazolo[4,3-c]quinazoline Derivatives

Asian Journal of Chemistry ◽

10.14233/ajchem.2020.22453 ◽

2020 ◽

Vol 32 (3) ◽

pp. 580-586

Author(s):

Ranjit V. Gadhave ◽

Bhanudas S. Kuchekar

Keyword(s):

Biological Evaluation ◽

Bacterial Strains ◽

Active Compounds ◽

Design Synthesis ◽

Structural Modifications ◽

E Coli ◽

Chemical Structures ◽

Ft Ir ◽

Antioxidant Agent

A new series of N-(benzo[d]thiazol-2-yl)-[1,2,4]triazolo[4,3-c]quinazoline-5-carboxamide derivatives were synthesized by condensation of [1,2,4]triazolo[4,3-c]quinazoline-5-carboxylate derivatives with substituted benzothiazoles. The chemical structures of the synthesized compounds were confirmed by FT-IR, MS and 1H NMR spectra. Designed triazoloquinazoline derivatives were docked with oxido-reductase enzyme (PDB Code 4h1j) and DNA gyrase enzyme (PDB Code 3g75). Based on high binding affinity score, the best compound were selected for synthesis and subjected to in vitro antioxidant and antibacterial activity. Compounds 7a and 7d were found to be most active compounds as antioxidant agent among this series when compared with ascorbic acid. Compounds 7a, 7d and 7f were found to be most active compounds as an antibacterial agents among this series when compared with ciprofloxacin against bacterial strains such as S. aureus (ATCC 25923), E. coli (ATCC 25922) and P. aeruginosa (ATCC 27853). Study revealed that the most active compounds after structural modifications can be exploited as lead molecules for other pharmacological activities such as anti-inflammatory, anticancer and antidepressant activities.

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Green Synthesis andIn VitroBiological Evaluation of Heteroaryl Chalcones and Pyrazolines of Medicinal Interest

Journal of Chemistry ◽

10.1155/2013/542973 ◽

2013 ◽

Vol 2013 ◽

pp. 1-4 ◽

Cited By ~ 2

Author(s):

Vishal Banewar

Keyword(s):

Green Synthesis ◽

Elemental Analysis ◽

Broad Spectrum ◽

Spectroscopic Data ◽

Heterocyclic Compounds ◽

Biological Activities ◽

Biological Evaluation ◽

Active Compounds

Pyrazolines are well known and important nitrogen containing 5-membered heterocyclic compounds. In the present investigation, a series of various heteroaryl chalcones and pyrazolines were synthesized by condensing formylquinolines with diverse ketones. The newly synthesized 2-pyrazolines were characterized on the basis of elemental analysis and spectroscopic data. All of the newly synthesized target compounds were selected by the NCI forin vitrobiological evaluation. These active compounds exhibited broad spectrum of various biological activities. Most of the compounds showed potent activity.

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