Synthesis, crystal structures and anti-inflammatory activity of four 3,5-bis(arylidene)-N-benzenesulfonyl-4-piperidone derivatives

2018 ◽  
Vol 74 (10) ◽  
pp. 1171-1179 ◽  
Author(s):  
Ning Li ◽  
Xianyong Bai ◽  
Lianshuang Zhang ◽  
Yun Hou
Keyword(s):  
Hydrogen Bonds ◽  
High Resolution Mass Spectrometry ◽  
Structural Characteristics ◽  
Crystal Structure Analysis ◽  
Inflammatory Activity ◽  
Unsaturated Ketone ◽  
Activity Data ◽  
Strong Electron ◽  
Phenyl Rings ◽  
Anti Inflammatory

3,5-Bis(arylidene)-4-piperidone (BAP) derivatives display good antitumour and anti-inflammatory activities because of their double α,β-unsaturated ketone structural characteristics. If N-benzenesulfonyl substituents are introduced into BAPs, the configuration of the BAPs would change significantly and their anti-inflammatory activities should improve. Four N-benzenesulfonyl BAPs, namely (3E,5E)-1-(4-methylbenzenesulfonyl)-3,5-bis[4-(trifluoromethyl)benzylidene]piperidin-4-one dichloromethane monosolvate, C28H21F6NO3S·CH2Cl2, (4), (3E,5E)-1-(4-fluorobenzenesulfonyl)-3,5-bis[4-(trifluoromethyl)benzylidene]piperidin-4-one, C27H18F7NO3S, (5), (3E,5E)-1-(4-nitrobenzenesulfonyl)-3,5-bis[4-(trifluoromethyl)benzylidene]piperidin-4-one, C27H18F6N2O5S, (6), and (3E,5E)-1-(4-cyanobenzenesulfonyl)-3,5-bis[4-(trifluoromethyl)benzylidene]piperidin-4-one dichloromethane monosolvate, C28H18F6N2O3S·CH2Cl2, (7), were prepared by Claisen–Schmidt condensation and N-sulfonylation. They were characterized by NMR, FT–IR and HRMS (high resolution mass spectrometry). Single-crystal structure analysis reveals that the two 4-(trifluoromethyl)phenyl rings on both sides of the piperidone ring in (4)–(7) adopt an E stereochemistry of the olefinic double bonds. Molecules of both (4) and (6) are connected by hydrogen bonds into one-dimensional chains. In (5) and (7), pairs of adjacent molecules embrace through intermolecular hydrogen bonds to form a bimolecular combination, which are further extended into a two-dimensional sheet. The anti-inflammatory activity data reveal that (4)–(7) significantly inhibit LPS-induced interleukin (IL-6) and tumour necrosis factor (TNF-α) secretion. Most importantly, (6) and (7), with strong electron-withdrawing substituents, display more potential inhibitory effects than (4) and (5).

Novel asymmetric 3,5-bis(arylidene)piperidin-4-one derivatives: synthesis, crystal structures and cytotoxicity

2018 ◽  
Vol 74 (6) ◽  
pp. 659-665 ◽  
Author(s):  
Binrong Yao ◽  
Ning Li ◽  
Chunhua Wang ◽  
Guige Hou ◽  
Qingguo Meng ◽  
...  
Keyword(s):  
Hydrogen Bonds ◽  
Cell Line ◽  
Antitumour Activity ◽  
Structural Characteristics ◽  
Crystal Structure Analysis ◽  
Unsaturated Ketone ◽  
Dimensional Network ◽  
Ft Ir ◽  
Hepatocellular Carcinoma Cell Line ◽  
Liver Hepatocellular Carcinoma

3,5-Bis(arylidene)piperidin-4-one derivatives (BAPs) display good antitumour activity because of their double α,β-unsaturated ketone structural characteristics. Reported BAPs have generally been symmetric and asymmetric BAPs have been little documented. Three asymmetric BAPs, namely (5E)-3-(4-tert-butylbenzylidene)-5-(4-fluorobenzylidene)-1-methylpiperidin-4-one, C24H26FNO, (5), (5E)-3-(4-tert-butylbenzylidene)-5-(3,5-dimethoxybenzylidene)-1-methylpiperidin-4-one, C26H31NO3, (6), and (5E)-3-{3-[(E)-(2,3-dihydroxybenzylidene)amino]benzylidene}-5-(2-fluorobenzylidene)-1-methylpiperidin-4-one, C27H23FN2O3, (12), were generated by Claisen–Schmidt condensation. They are characterized by NMR and FT–IR spectroscopies, and elemental analysis. Single-crystal structure analysis reveals that the two arylidene rings on both sides of the BAP structures adopt an E stereochemistry of the olefinic double bonds and the compounds are E,E isomers. Molecules of (5) and (12) generate one-dimensional chains through intermolecular hydrogen bonds, while compound (6) generates a two-dimensional network through hydrogen bonds. Preliminary cytotoxicities toward human liver hepatocellular carcinoma cell line (HepG2), human acute mononuclear granulocyte leukaemia (THP-1) and human normal hepatical cell line (LO2) were evaluated.

scholarly journals Thiophene-Based Compounds with Potential Anti-Inflammatory Activity

2021 ◽  
Vol 14 (7) ◽  
pp. 692
Author(s):  
Ryldene Marques Duarte da Cruz ◽  
Francisco Jaime Bezerra Mendonça-Junior ◽  
Natália Barbosa de Mélo ◽  
Luciana Scotti ◽  
Rodrigo Santos Aquino de Araújo ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Structural Characteristics ◽  
Tiaprofenic Acid ◽  
Inflammatory Activity ◽  
Drug Candidates ◽  
Biological Target ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Privileged Structures

Rheumatoid arthritis, arthrosis and gout, among other chronic inflammatory diseases are public health problems and represent major therapeutic challenges. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most prescribed clinical treatments, despite their severe side effects and their exclusive action in improving symptoms, without effectively promoting the cure. However, recent advances in the fields of pharmacology, medicinal chemistry, and chemoinformatics have provided valuable information and opportunities for development of new anti-inflammatory drug candidates. For drug design and discovery, thiophene derivatives are privileged structures. Thiophene-based compounds, like the commercial drugs Tinoridine and Tiaprofenic acid, are known for their anti-inflammatory properties. The present review provides an update on the role of thiophene-based derivatives in inflammation. Studies on mechanisms of action, interactions with receptors (especially against cyclooxygenase (COX) and lipoxygenase (LOX)), and structure-activity relationships are also presented and discussed. The results demonstrate the importance of thiophene-based compounds as privileged structures for the design and discovery of novel anti-inflammatory agents. The studies reveal important structural characteristics. The presence of carboxylic acids, esters, amines, and amides, as well as methyl and methoxy groups, has been frequently described, and highlights the importance of these groups for anti-inflammatory activity and biological target recognition, especially for inhibition of COX and LOX enzymes.

scholarly journals Pyrrolizine-5-carboxamides: Exploring the impact of various substituents on anti-inflammatory and anticancer activities

2018 ◽  
Vol 68 (3) ◽  
pp. 251-273 ◽  
Author(s):  
Ahmed M. Gouda ◽  
Ahmed H. Abdelazeem ◽  
Ashraf N. Abdalla ◽  
Muhammad Ahmed
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Inflammatory Activity ◽  
Electronic Effects ◽  
Anticancer Activities ◽  
Phenyl Rings ◽  
Anti Inflammatory ◽  
New Compounds ◽  
The Impact ◽  
Mcf 7

Abstract Towards optimization of the pyrrolizine-5-carboxamide scaffold, a novel series of six derivatives (4a-c and 5a-c) was prepared and evaluated for their anti-inflammatory, analgesic and anticancer activities. The (EZ)-7-cyano-6-((4-hydroxybenzylidene)amino)-N-(p-tolyl)-2,3-dihydro-1H-pyrrolizine-5-carboxamide (4b) and (EZ)-6-((4-chlorobenzylidene)-amino)-7-cyano-N-(p-tolyl)-2,3-dihydro-1H-pyrrolizine-5-carboxamide (5b) bearing the electron donating methyl group showed the highest anti-inflammatory activity while (EZ)-6-((4-chlorobenzylidene)amino)-7-cyano-N-phenyl-2,3-dihydro-1H-pyrrolizine-5-carboxamide (5a) was the most active analgesic agent. Cytotoxicity of the new compounds was evaluated against the MCF-7, A2780 and HT29 cancer cell lines using the MTT assay. Compounds 4b and 5b displayed high anticancer activity with IC50 in the range of 0.30–0.92 μmol L−1 against the three cell lines, while compound (EZ)-N-(4-chlorophenyl)-7-cyano-6-((4-hydroxybenzylidene)-amino)-2,3-dihydro-1H-pyrrolizine-5-carboxamide (4c) was the most active against MCF-7 cells (IC50 = 0.08 μmol L−1). Both the anti-inflammatory and anticancer activities of the new compounds were dependent on the type of substituent on the phenyl rings. Substituents with opposite electronic effects on the two phenyl rings are preferable for high cytotoxicity against the MCF-7 and A2780 cells. COX inhibition was suggested as the molecular mechanism of the anti-inflammatory activity of the new compounds while no clear relationship could be observed between COX inhibition and anticancer activity. Compound 5b, the most active against the three cell lines, induced dose-dependent early apoptosis with 0.1–0.2 % necrosis in MCF-7 cells. New compounds showed promising drug-likeness scores while the docking study revealed high binding affinity to COX-2. Taken together, this study highlighted the significant impact of the substituents on the anti-inflammatory and anticancer activity of pyrrolizine-5-carboxamides, which could help in further optimization to discover good leads for the treatment of cancer and inflammation.

The fixed structure of Licochalcone A by α, β-unsaturated ketone is necessary for anti-inflammatory activity through the inhibition of NF-κB activation

2010 ◽  
Vol 10 (5) ◽  
pp. 562-571 ◽  
Author(s):  
Megumi Funakoshi-Tago ◽  
Kei Nakamura ◽  
Rina Tsuruya ◽  
Masashi Hatanaka ◽  
Tadahiko Mashino ◽  
...  
Keyword(s):  
Inflammatory Activity ◽  
Unsaturated Ketone ◽  
Licochalcone A ◽  
Anti Inflammatory ◽  
Fixed Structure

scholarly journals Antioxidant and Anti-Inflammatory Activity of Cynanchum acutum L. Isolated Flavonoids Using Experimentally Induced Type 2 Diabetes Mellitus: Biological and In Silico Investigation for NF-κB Pathway/miR-146a Expression Modulation

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1713
Author(s):  
Reda F. A. Abdelhameed ◽  
Amany K. Ibrahim ◽  
Mahmoud A. Elfaky ◽  
Eman S. Habib ◽  
Mayada I. Mahamed ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
High Resolution Mass Spectrometry ◽  
Antioxidant Properties ◽  
Serum Levels ◽  
Inflammatory Activity ◽  
Bioactive Metabolites ◽  
Biological Investigation ◽  
Anti Inflammatory

Cynanchum acutum L. is a climbing vine that belongs to the family Apocynaceae. Using different chromatographic techniques, seven compounds were isolated from the methanolic extract of the plant. The isolated compounds include six flavonoid compounds identified as rutin (1), quercetin-3-O-neohesperidoside (2), quercetin-3-O-β-galactoside (3), isoquercitrin (4), quercetin (5), and kaempferol 3-O-β-glucoside (6), in addition to a coumarin, scopoletin (7). The structures of the compounds were elucidated based on 1D NMR spectroscopy and high-resolution mass spectrometry (HR-MS), and by comparison with data reported in the literature. The first five compounds were selected for in vivo investigation of their anti-inflammatory and antioxidant properties in a rat model of type 2 diabetes. All tested compounds significantly reduced oxidative stress and increased erythrocyte lysate levels of antioxidant enzymes, along with the amelioration of the serum levels of inflammatory markers. Upregulation of miR-146a expression and downregulation of nuclear factor kappa B (NF-κB) expression were detected in the liver and adipose tissue of rats treated with the isolated flavonoids. Results from the biological investigation and those from the validated molecular modeling approach on two biological targets of the NF-κB pathway managed to highlight the superior anti-inflammatory activity of quercetin-3-O-galactoside (3) and quercetin (5), as compared to other bioactive metabolites.

Gabapentin Antioxidant Derivatives with Anti-Inflammatory and Neuroprotective Potency

2021 ◽  
Vol 18 ◽  
Author(s):  
Georgios Papagiouvannis ◽  
Panagiotis Theodosis-Nobelos ◽  
Paraskevi Tziona ◽  
Antonios Gavalas ◽  
Panos N. Kourounakis ◽  
...  
Keyword(s):  
Structural Characteristics ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Protein Glycation ◽  
Inflammatory Activity ◽  
Biochemical Pathways ◽  
Rat Paw Edema ◽  
Anti Inflammatory ◽  
Effective Drugs

Aims: The aim of this work is to investigate the antioxidant and anti-inflammatory potency of novel gabapentin derivatives, which could be proven useful as neuroprotective agents. Background: Alzheimer’s Disease (AD) is one of the most common neurodegenerative disorders worldwide. Due to its multi-factorial character, no effective treatment has been obtained yet. In this direction, the multi-targeting compounds approach could be useful for the development of novel, more effective drugs against AD. Oxidative stress and inflammation are highly involved in the progression of neurodegeneration, while gabapentin has been investigated for the treatment of behavioral symptoms in AD. Objective: In this work, derivatives of cinnamic acid, trolox and 3,5-di-tertbutyl-4-hydroxybenzoic acid amidated with gabapentin methyl ester, were designed and studied. Compounds with these structural characteristics are expected to act in various biochemical pathways, affecting neurodegenerative processes. Methods: The designed compounds were synthesized with classical amidation methods, purified by flash column chromatography, and identified spectrometrically (1H-NMR and 13C-NMR). Their purity was determined by CHN elemental analysis. They were tested in vitro for their antioxidant and anti-inflammatory properties, and for their inhibitory effect on acetylcholinesterase. Their in vivo anti-inflammatory activity was also tested. Results: Those molecules incorporating an antioxidant moiety possessed inhibitory activity against rat microsomal membrane lipid peroxidation and oxidative protein glycation, as well as radical scavenging activity. Moreover, most of them presented moderate inhibition towards lipoxygenase (up to 51% at 100μΜ) and acetylcholinesterase (AchE) (IC50 up to 274μΜ) activities. Finally, all synthesized compounds presented in vivo anti-inflammatory activity, decreasing carrageenan-induced rat paw edema up to 53% and some of them could inhibit cyclooxygenase significantly. Conclusion: These results indicate that the designed compounds could be proven useful as multi-targeting molecules against AD, since they affect various biochemical pathways associated with neurodegeneration. Thus, more effective drugs can be obtained, and possible adverse effects of drug combination can be limited.

Structural Characteristics of a Bioactive Polysaccharide from Sorghum arundinaceum

2003 ◽  
Vol 58 (5-6) ◽  
pp. 342-346 ◽  
Author(s):  
Bernadete P. da Silva ◽  
Graziela M. Silva ◽  
José P. Parente
Keyword(s):  
Molecular Weight ◽  
Capillary Permeability ◽  
Structural Characteristics ◽  
Apparent Molecular Weight ◽  
Spectroscopic Studies ◽  
Type Structure ◽  
Inflammatory Activity ◽  
Branching Points ◽  
Anti Inflammatory ◽  
Permeability Assay

AbstractA polysaccharide, an α-ᴅ -glucan with an apparent molecular weight of 6.85×104, called PSa glucan, was isolated from fresh seeds of Sorghum arundinaceum by fractionation on Sephacryl S-300 HR and Sephadex G-25. Chemical and spectroscopic studies indicated that it has a highly branched glucan type structure composed of α-(154) linked d-glucopyranose residues with (1→3), (1→6) branching points, and a significant amount of α-(1→6) branching to α-(1→3) linked ᴅ -glucopyranose residues. The anti-inflammatory activity of the polysaccharide was performed using the capillary permeability assay.

Synthesis, crystal structures and anti-inflammatory activity of fluorine-substituted 1,4,5,6-tetrahydrobenzo[h]quinazolin-2-amine derivatives

2019 ◽  
Vol 75 (8) ◽  
pp. 1157-1165 ◽  
Author(s):  
Yue Sun ◽  
Zhongfei Gao ◽  
Chunhua Wang ◽  
Guige Hou
Keyword(s):  
Hydrogen Bonds ◽  
Guanidine Hydrochloride ◽  
Chloride Ion ◽  
Inflammatory Activity ◽  
Buffer System ◽  
X Ray Diffraction ◽  
Hydrogen Bond Acceptor ◽  
Unsaturated Ketones ◽  
3D Network ◽  
Anti Inflammatory

Two fluorine-substituted 1,4,5,6-tetrahydrobenzo[h]quinazolin-2-amine (BQA) derivatives, namely 2-amino-4-(2-fluorophenyl)-9-methoxy-1,4,5,6-tetrahydrobenzo[h]quinazolin-3-ium chloride, (8), and 2-amino-4-(4-fluorophenyl)-9-methoxy-1,4,5,6-tetrahydrobenzo[h]quinazolin-3-ium chloride, (9), both C19H19FN3O+·Cl−, were generated by Michael addition reactions between guanidine hydrochloride and the α,β-unsaturated ketones (E)-2-(2-fluorobenzylidene)-7-methoxy-3,4-dihydronaphthalen-1(2H)-one, C18H15FO2, (6), and (E)-2-(4-fluorobenzylidene)-7-methoxy-3,4-dihydronaphthalen-1(2H)-one, (7). Because both sides of α,β-unsaturated ketones (6) or (7) can be attacked by guanidine, we obtained a pair of isomers in (8) and (9). Single-crystal X-ray diffraction indicates that each isomer has a chiral C atom and both (8) and (9) crystallize in the achiral space group P21/c. The chloride ion, as a hydrogen-bond acceptor, plays an important role in the formation of multiple hydrogen bonds. Thus, adjacent molecules are connected through intermolecular hydrogen bonds to generate a banded structure. Furthermore, these bands are linked into an interesting 3D network via hydrogen bonds and π–π interactions. Fortunately, the solubilities of (8) and (9) were distinctly improved and can exceed 50 mg ml−1 in water or PBS buffer system (pH 7.4) at room temperature. In addition, the results of an investigation of anti-inflammatory activity show that (8) and (9), with o- and p-fluoro substituents, respectively, display more potential for inhibitory effects on LPS-induced NO secretion than starting ketones (6) and (7).

Sign in / Sign up

Export Citation Format

Share Document