scholarly journals Hydrazones of 4-(Trifluoromethyl)benzohydrazide as New Inhibitors of Acetyl- and Butyrylcholinesterase

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 989
Author(s):  
Martin Krátký ◽  
Katarína Svrčková ◽  
Quynh Anh Vu ◽  
Šárka Štěpánková ◽  
Jarmila Vinšová
Keyword(s):  
Biological Activity ◽  
Mixed Type ◽  
Cholinesterase Inhibitors ◽  
Eukaryotic Cell ◽  
Structure Activity ◽  
Aliphatic Ketones ◽  
Ic50 Values ◽  
Central Nervous Systems ◽  
Dual Inhibition ◽  
Potential Inhibitors

Based on the broad spectrum of biological activity of hydrazide–hydrazones, trifluoromethyl compounds, and clinical usage of cholinesterase inhibitors, we investigated hydrazones obtained from 4-(trifluoromethyl)benzohydrazide and various benzaldehydes or aliphatic ketones as potential inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). They were evaluated using Ellman’s spectrophotometric method. The hydrazide–hydrazones produced a dual inhibition of both cholinesterase enzymes with IC50 values of 46.8–137.7 µM and 19.1–881.1 µM for AChE and BuChE, respectively. The majority of the compounds were stronger inhibitors of AChE; four of them (2-bromobenzaldehyde, 3-(trifluoromethyl)benzaldehyde, cyclohexanone, and camphor-based 2o, 2p, 3c, and 3d, respectively) produced a balanced inhibition of the enzymes and only 2-chloro/trifluoromethyl benzylidene derivatives 2d and 2q were found to be more potent inhibitors of BuChE. 4-(Trifluoromethyl)-N’-[4-(trifluoromethyl)benzylidene]benzohydrazide 2l produced the strongest inhibition of AChE via mixed-type inhibition determined experimentally. Structure–activity relationships were identified. The compounds fit physicochemical space for targeting central nervous systems with no apparent cytotoxicity for eukaryotic cell line together. The study provides new insights into this CF3-hydrazide–hydrazone scaffold.

scholarly journals Novel Aminoguanidine Hydrazone Analogues: From Potential Antimicrobial Agents to Potent Cholinesterase Inhibitors

2021 ◽  
Vol 14 (12) ◽  
pp. 1229
Author(s):  
Martin Krátký ◽  
Šárka Štěpánková ◽  
Klára Konečná ◽  
Katarína Svrčková ◽  
Jana Maixnerová ◽  
...  
Keyword(s):  
Mixed Type ◽  
Cholinesterase Inhibitors ◽  
Antimicrobial Agents ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Trichophyton Mentagrophytes ◽  
Substitution Pattern ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Ic50 Values ◽  
Further Development

A series of thirty-one hydrazones of aminoguanidine, nitroaminoguanidine, 1,3-diaminoguanidine, and (thio)semicarbazide were prepared from various aldehydes, mainly chlorobenzaldehydes, halogenated salicylaldehydes, 5-nitrofurfural, and isatin (yields of 50–99%). They were characterized by spectral methods. Primarily, they were designed and evaluated as potential broad-spectrum antimicrobial agents. The compounds were effective against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus with minimum inhibitory concentrations (MIC) from 7.8 µM, as well as Gram-negative strains with higher MIC. Antifungal evaluation against yeasts and Trichophyton mentagrophytes found MIC from 62.5 µM. We also evaluated inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The compounds inhibited both enzymes with IC50 values of 17.95–54.93 µM for AChE and ≥1.69 µM for BuChE. Based on the substitution, it is possible to modify selectivity for a particular cholinesterase as we obtained selective inhibitors of either AChE or BuChE, as well as balanced inhibitors. The compounds act via mixed-type inhibition. Their interactions with enzymes were studied by molecular docking. Cytotoxicity was assessed in HepG2 cells. The hydrazones differ in their toxicity (IC50 from 5.27 to >500 µM). Some of the derivatives represent promising hits for further development. Based on the substitution pattern, it is possible to modulate bioactivity to the desired one.

scholarly journals Synthesis and Bioactivity of Thiazolethioacetamides as Potential Metallo-β-Lactamase Inhibitors

Antibiotics ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 99 ◽  
Author(s):  
Yi-Lin Zhang ◽  
Yong Yan ◽  
Xue-Jun Wang ◽  
Ke-Wu Yang
Keyword(s):  
Antibacterial Activity ◽  
Antibiotic Resistance ◽  
Biological Activity ◽  
Inhibitory Activity ◽  
Crucial Role ◽  
Aromatic Substituent ◽  
Bacterial Diseases ◽  
Structure Activity ◽  
Ic50 Values ◽  
Molecule Docking

Metallo-β-lactamase (MβLs) mediated antibiotic resistance seriously threatens the treatment of bacterial diseases. Recently, we found that thioacetamides can be a potential MβL inhibitor skeleton. In order to improve the information of the skeleton, twelve new thiazolethioacetamides were designed by modifying the aromatic substituent. Biological activity assays identify the thiazolethioacetamides can inhibit ImiS with IC50 values of 0.17 to 0.70 μM. For two of them, the IC50 values against VIM-2 were 2.2 and 19.2 μM, which is lower than in our previous report. Eight of the thiazolethioacetamides are able to restore antibacterial activity of cefazolin against E.coli-ImiS by 2–4 fold. An analysis of the structure–activity relation and molecule docking show that the style and position of electron withdrawing groups in aromatic substituents play a crucial role in the inhibitory activity of thiazolethioacetamides. These results indicate that thiazolethioacetamides can serve as a potential skeleton of MβL inhibitors.

Biological Activity of Trans-Membrane Anion Carriers

2018 ◽  
Vol 25 (30) ◽  
pp. 3560-3576 ◽  
Author(s):  
Massimo Tosolini ◽  
Paolo Pengo ◽  
Paolo Tecilla
Keyword(s):  
Biological Activity ◽  
Membrane Transport ◽  
Anticancer Agents ◽  
Biological Effects ◽  
Structure Activity Relationship ◽  
New Drugs ◽  
Activity Relationship ◽  
Anion Channels ◽  
Cellular Homeostasis ◽  
Structure Activity

Natural and synthetic anionophores promote the trans-membrane transport of anions such as chloride and bicarbonate. This process may alter cellular homeostasis with possible effects on internal ions concentration and pH levels triggering several and diverse biological effects. In this article, an overview of the recent results on the study of aniontransporters, mainly acting with a carrier-type mechanism, is given with emphasis on the structure/activity relationship and on their biological activity as antibiotic and anticancer agents and in the development of new drugs for treating conditions derived from dysregulation of natural anion channels.

Neurotoxicity of Pesticides: The Roadmap for the Cubic Mode of Action

2020 ◽  
Vol 27 (1) ◽  
pp. 54-77 ◽  
Author(s):  
Bogdan Bumbăcilă ◽  
Mihai V. Putz
Keyword(s):  
Biological Activity ◽  
Wiener Index ◽  
Laboratory Animals ◽  
Covalent Bonds ◽  
Organophosphate Compounds ◽  
Sar Studies ◽  
Structure Activity ◽  
Cubic Structure

Pesticides are used today on a planetary-wide scale. The rising need for substances with this biological activity due to an increasing consumption of agricultural and animal products and to the development of urban areas makes the chemical industry to constantly investigate new molecules or to improve the physicochemical characteristics, increase the biological activities and improve the toxicity profiles of the already known ones. Molecular databases are increasingly accessible for in vitro and in vivo bioavailability studies. In this context, structure-activity studies, by their in silico - in cerebro methods, are used to precede in vitro and in vivo studies in plants and experimental animals because they can indicate trends by statistical methods or biological activity models expressed as mathematical equations or graphical correlations, so a direction of study can be developed or another can be abandoned, saving financial resources, time and laboratory animals. Following this line of research the present paper reviews the Structure-Activity Relationship (SAR) studies and proposes a correlation between a topological connectivity index and the biological activity or toxicity made as a result of a study performed on 11 molecules of organophosphate compounds, randomly chosen, with a basic structure including a Phosphorus atom double bounded to an Oxygen atom or to a Sulfur one and having three other simple covalent bonds with two alkoxy (-methoxy or -ethoxy) groups and to another functional group different from the alkoxy groups. The molecules were packed on a cubic structure consisting of three adjacent cubes, respecting a principle of topological efficiency, that of occupying a minimal space in that cubic structure, a method that was called the Clef Method. The central topological index selected for correlation was the Wiener index, since it was possible this way to discuss different adjacencies between the nodes in the graphs corresponding to the organophosphate compounds molecules packed on the cubic structure; accordingly, "three dimensional" variants of these connectivity indices could be considered and further used for studying the qualitative-quantitative relationships for the specific molecule-enzyme interaction complexes, including correlation between the Wiener weights (nodal specific contributions to the total Wiener index of the molecular graph) and the biochemical reactivity of some of the atoms. Finally, when passing from SAR to Q(uantitative)-SAR studies, especially by the present advanced method of the cubic molecule (Clef Method) and its good assessment of the (neuro)toxicity of the studied molecules and of their inhibitory effect on the target enzyme - acetylcholinesterase, it can be seen that a predictability of the toxicity and activity of different analogue compounds can be ensured, facilitating the in vivo experiments or improving the usage of pesticides.

Synthesis and Antitumor Activity Evaluation of New Phenanthrene-Based Tylophorine Derivatives

2019 ◽  
Vol 16 (6) ◽  
pp. 462-467
Author(s):  
Songtao Li ◽  
Hongling Zhao ◽  
Zhifeng Yin ◽  
Shuhua Deng ◽  
Yang Gao ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Lines ◽  
Antitumor Activities ◽  
Human Carcinoma ◽  
Carcinoma Cell Lines ◽  
Structure Activity ◽  
Human Carcinoma Cell ◽  
Ic50 Values ◽  
Relationship Of

A series of new phenanthrene-based tylophorine derivatives (PBTs) were synthesized in good yield and their structures were characterized by 1H-NMR spectroscopy and ESI MS. In vitro antitumor activity of these compounds against five human carcinoma cell lines, including HCT116 (colorectal), BGC-823 (gastric), HepG-2 (hepatic), Hela (cervical) and H460 (lung) cells, was evaluated by MTT assay. Among these PBTs, compound 6b showed the highest antitumor activities against HCT116 and HepG-2 cell lines with IC50 values of 6.1 and 6.4 μM, respectively, which were comparable to that of adriamycin hydrochloride. The structure-activity relationship of these compounds was also discussed based on the results of their antitumor activity.

Cytotoxic Constituents from the Bark of Erythrina poeppigiana Against the MCF-7 Breast Cancer Cell Lines

2020 ◽  
Vol 10 (3) ◽  
pp. 257-261
Author(s):  
Tati Herlina ◽  
Merlin ◽  
Mohd. Azlan ◽  
Unang Supratman
Keyword(s):  
Breast Cancer ◽  
Cytotoxic Activity ◽  
Chemical Structure ◽  
Breast Cancer Cell Lines ◽  
Erythrina Poeppigiana ◽  
Structure Activity ◽  
Cancer Line ◽  
Cytotoxic Compounds ◽  
Ic50 Values ◽  
Mcf 7

Background: Erythrina poeppigiana (Leguminosae) is a high-growing plant with an orange flower that is widely distributed in tropical and subtropical countries. This particular plant is widely used in traditional medicine for gynecological complications and the treatment of various diseases. There exists no previous information regarding cytotoxic compounds from this plant. Objective: This research is to isolate cytotoxic compounds from E. poeppigiana. Methods: The isolation step was carried out using a combination of chromatographic techniques to obtain isolated three compounds (1, 2, and 3). Results: The chemical structure of isolated compounds was elucidated by spectroscopic methods and identified as β-erythroidine (1), 8-oxo-β-erythroidine (2), and 8-oxo-α-erythroidine (3). Compounds (1-3) showed cytotoxic activity against MCF-7 breast cancer line with IC50 values of 36.8, 60.8 and 875.4 μM, respectively. Conclusion: Three compounds have been successfully isolated from Erythrina poeppigiana (Leguminosae), showing cytotoxic properties against MCF-7 breast cancer line. Structure-activity relationship studies showed that the presence of enone moiety on compound 1 can reduce its cytotoxic activity towards MCF-7 breast cancer line.

Studies on the EC50 of Natural Monoterpenes as Fungal Inhibitors with Quantitative Structure-Activity Relationships (QSARs)

2020 ◽  
Vol 10 (1) ◽  
pp. 44-60
Author(s):  
Mohamed E.I. Badawy ◽  
Entsar I. Rabea ◽  
Samir A.M. Abdelgaleil
Keyword(s):  
Biological Activity ◽  
Plant Pathogens ◽  
Molecular Descriptors ◽  
Microbial Pathogens ◽  
Quantitative Structure ◽  
Qsar Study ◽  
Qsar Analysis ◽  
Pharmacophore Modelling ◽  
Structure Activity ◽  
Wide Range

Background:Monoterpenes are the main constituents of the essential oils obtained from plants. These natural products offered wide spectra of biological activity and extensively tested against microbial pathogens and other agricultural pests.Methods:Antifungal activity of 10 monoterpenes, including two hydrocarbons (camphene and (S)- limonene) and eight oxygenated hydrocarbons ((R)-camphor, (R)-carvone, (S)-fenchone, geraniol, (R)-linalool, (+)-menthol, menthone, and thymol), was determined against fungi of Alternaria alternata, Botrytis cinerea, Botryodiplodia theobromae, Fusarium graminearum, Phoma exigua, Phytophthora infestans, and Sclerotinia sclerotiorum by the mycelia radial growth technique. Subsequently, Quantitative Structure-Activity Relationship (QSAR) analysis using different molecular descriptors with multiple regression analysis based on systematic search and LOOCV technique was performed. Moreover, pharmacophore modelling was carried out using LigandScout software to evaluate the common features essential for the activity and the hypothetical geometries adopted by these ligands in their most active forms.Results:The results showed that the antifungal activities were high, but depended on the chemical structure and the type of microorganism. Thymol showed the highest effect against all fungi tested with respective EC50 in the range of 10-86 mg/L. The QSAR study proved that the molecular descriptors HBA, MR, Pz, tPSA, and Vp were correlated positively with the biological activity in all of the best models with a correlation coefficient (r) ≥ 0.98 and cross-validated values (Q2) ≥ 0.77.Conclusion:The results of this work offer the opportunity to choose monoterpenes with preferential antimicrobial activity against a wide range of plant pathogens.

scholarly journals The Inhibitory Effects of Plant Derivate Polyphenols on the Main Protease of SARS Coronavirus 2 and Their Structure–Activity Relationship

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1924
Author(s):  
Thi Thanh Hanh Nguyen ◽  
Jong-Hyun Jung ◽  
Min-Kyu Kim ◽  
Sangyong Lim ◽  
Jae-Myoung Choi ◽  
...  
Keyword(s):  
Structure Activity Relationship ◽  
Garlic Extract ◽  
Activity Relationship ◽  
Hydroxyl Group ◽  
Inhibitory Effects ◽  
Structure Activity ◽  
Main Protease ◽  
Ic50 Values ◽  
Km Value ◽  
Novel Coronavirus

The main protease (Mpro) is a major protease having an important role in viral replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus that caused the pandemic of 2020. Here, active Mpro was obtained as a 34.5 kDa protein by overexpression in E. coli BL21 (DE3). The optimal pH and temperature of Mpro were 7.5 and 37 °C, respectively. Mpro displayed a Km value of 16 μM with Dabcyl-KTSAVLQ↓SGFRKME-Edans. Black garlic extract and 49 polyphenols were studied for their inhibitory effects on purified Mpro. The IC50 values were 137 μg/mL for black garlic extract and 9–197 μM for 15 polyphenols. The mixtures of tannic acid with puerarin, daidzein, and/or myricetin enhanced the inhibitory effects on Mpro. The structure–activity relationship of these polyphenols revealed that the hydroxyl group in C3′, C4′, C5′ in the B-ring, C3 in the C-ring, C7 in A-ring, the double bond between C2 and C3 in the C-ring, and glycosylation at C8 in the A-ring contributed to inhibitory effects of flavonoids on Mpro.

scholarly journals Fusarins G–L with Inhibition of NO in RAW264.7 from Marine-Derived Fungus Fusarium solani 7227

Marine Drugs ◽  
2021 ◽  
Vol 19 (6) ◽  
pp. 305
Author(s):  
Guangyuan Luo ◽  
Li Zheng ◽  
Qilin Wu ◽  
Senhua Chen ◽  
Jing Li ◽  
...  
Keyword(s):  
Fusarium Solani ◽  
2D Nmr ◽  
Inflammatory Activity ◽  
Raw264.7 Cells ◽  
Spectroscopic Methods ◽  
X Ray ◽  
X Ray Crystallography ◽  
Structure Activity ◽  
Ic50 Values ◽  
New Compounds

Six new fusarin derivatives, fusarins G–L (1–6), together with five known compounds (5–11) were isolated from the marine-derived fungus Fusarium solani 7227. The structures of the new compounds were elucidated by means of comprehensive spectroscopic methods (1D and 2D NMR, HRESIMS, ECD, and ORC) and X-ray crystallography. Compounds 5–11 exhibited potent anti-inflammatory activity by inhibiting the production of NO in RAW264.7 cells activated by lipopolysaccharide, with IC50 values ranging from 3.6 to 32.2 μM. The structure–activity relationships of the fusarins are discussed herein.

scholarly journals The Psychonauts’ Benzodiazepines; Quantitative Structure-Activity Relationship (QSAR) Analysis and Docking Prediction of Their Biological Activity

2021 ◽  
Vol 14 (8) ◽  
pp. 720
Author(s):  
Valeria Catalani ◽  
Michelle Botha ◽  
John Martin Corkery ◽  
Amira Guirguis ◽  
Alessandro Vento ◽  
...  
Keyword(s):  
Biological Activity ◽  
Computational Models ◽  
Quantitative Structure Activity Relationship ◽  
Structure Activity Relationship ◽  
Docking Studies ◽  
Health Concern ◽  
Activity Relationship ◽  
Quantitative Structure ◽  
High Biological Activity ◽  
Structure Activity

Designer benzodiazepines (DBZDs) represent a serious health concern and are increasingly reported in polydrug consumption-related fatalities. When new DBZDs are identified, very limited information is available on their pharmacodynamics. Here, computational models (i.e., quantitative structure-activity relationship/QSAR and Molecular Docking) were used to analyse DBZDs identified online by an automated web crawler (NPSfinder®) and to predict their possible activity/affinity on the gamma-aminobutyric acid A receptors (GABA-ARs). The computational software MOE was used to calculate 2D QSAR models, perform docking studies on crystallised GABA-A receptors (6HUO, 6HUP) and generate pharmacophore queries from the docking conformational results. 101 DBZDs were identified online by NPSfinder®. The validated QSAR model predicted high biological activity values for 41% of these DBDZs. These predictions were supported by the docking studies (good binding affinity) and the pharmacophore modelling confirmed the importance of the presence and location of hydrophobic and polar functions identified by QSAR. This study confirms once again the importance of web-based analysis in the assessment of drug scenarios (DBZDs), and how computational models could be used to acquire fast and reliable information on biological activity for index novel DBZDs, as preliminary data for further investigations.

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