Synthesis and biological activity of new anti-inflammatory compounds containing the 1,4-benzodioxine and/or pyrrole system

Harrak, Youssef; Rosell, Glòria; Daidone, Giuseppe; Plescia, Salvatore; Schillaci, Domenico; Pujol, Maria Dolors

doi:10.1016/j.bmc.2007.04.050

Cited by 83 publications

(33 citation statements)

References 27 publications

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“…Fourteen of the synthesized compounds were evaluated for their anti-inflammatory activity, using a method established by Harrk et al 31 4-benzodioxine or pyrrole nucleus are described. All the newly synthesized compounds were examined for their in vitro and in vivo anti-inflammatory activity.…”

Section: Biological Results and Discussionmentioning

confidence: 99%

“…32,74,79,80 First, the structure should consist of an acidic moiety (carboxylic acid, enols, ester etc.) attached to a planar, aromatic functional group (appears to correlate with the double bond of AA), 31 4-benzodioxine or pyrrole nucleus are described. All the newly synthesized compounds were examined for their in vitro and in vivo anti-inflammatory activity.…”

Section: Structure-activity Relationships (Sar)mentioning

confidence: 99%

“…[23][24][25][26][27][28] Pyrrolylacetic acid derivatives such as tolmetin (Rumatol ® ) and zomepirac (Zomax ® ) were proved to be NSAIDs 6 with strong anti-inflammatory activity. 29,30 Other pyrrole and fused pyrrole compounds have been recently reported as potent COX-1 and COX-2 inhibitors: 31,32 4-benzodioxine or pyrrole nucleus are described. All the newly synthesized compounds were examined for their in vitro and in vivo anti-inflammatory activity.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and Structure Activity Relationship of Some Indole Derivatives as Potential Anti-inflammatory Agents

Fatahala

Khedr

Mohamed

2017

ACSi

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A series of fused pyrroles were synthesized and tested for their in vivo anti-inflammatory activity. Among 14 examined derivatives, 5 derivatives (1b-e, g and 5b), showed a promising anti-inflammatory activity equivalent to reference anti-inflammatory drugs (indomethacin and ibuprofen). A molecular docking study was conducted to interpret the biological activities of the tested compounds. The docking results were complementary with the phase of the biological survey and confirmed the biological effects.

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Section: Biological Results and Discussionmentioning

confidence: 99%

Section: Structure-activity Relationships (Sar)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthesis and Structure Activity Relationship of Some Indole Derivatives as Potential Anti-inflammatory Agents

Fatahala

Khedr

Mohamed

2017

ACSi

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“…It can also be acquired from more common natural sources. [13][14][15][16][17] It was reported that various derivatives of 1,4-benzodioxan show biological activities, [18][19][20] some of which are anticancer agents 21) or new anti-inflammatory compounds.…”

Section: )mentioning

confidence: 99%

Synthesis and Antibacterial Activity of Cinnamaldehyde Acylhydrazone with a 1,4-Benzodioxan Fragment as a Novel Class of Potent β-Ketoacyl–Acyl Carrier Protein Synthase III (FabH) Inhibitor

et al. 2014

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Fatty acid biosynthesis is essential for bacterial survival. β-Ketoacyl-acyl carrier protein (ACP) synthase III (FabH), is a particularly attractive antibacterial target, since it is central to the initiation of fatty acid biosynthesis. Three series of 21 cinnamaldehyde acylhydrazone derivatives, A3-9, B3-9, and C3-9, were synthesized and evaluated for FabH-inhibitory activity. Compound B6 showed the most potent biological activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis (minimum inhibitory concentrations (MICs) values: 1.56-3.13 µg/mL) and was comparable with the positive control. Docking simulation by positioning compound B6 in the FabH structure active site was performed to explore the possible binding model. Key words cinnamaldehyde; acylhydrazone; benzodioxan; antibacterial; structure-activity relationship; FabH inhibitor Bactria has become a greater threat to human beings as antibiotic resistance sweeps the world.1) Fatty acid biosynthesis (FAB) is an essential metabolic process for prokaryotic organisms and is required for cell viability and growth.2) The significant differences between human and prokaryotic FAB systems render prokaryotic FAB to be an attractive target.3)The β-ketoacyl-acyl carrier protein (ACP) synthase III (FabH) has no homologs in human and is one of essential functional enzymes in bacterial FAB system. FabH initiates the FAB cycle by catalyzing the first condensation step between acetylCoA and malonyl-ACP, playing a key regulatory role in the bacterial FAB cycle.4) Many kinds of compounds harbored Schiff base motif or hydrozone motif was screened for antimicrobial activity, some of which are potent inhibitors of FabH. 5)For example, compounds 1-8 (Fig. 1A) reported as inhibitors of Escherichia coli FabH showed the most potent FabH inhibitory activity in each article respectively. [6][7][8][9][10][11][12] 1,4-Benzodioxan is an important frame for medicine and widely found in natural products, e.g. silybin, purpurenol, 3,4-dihydroxystyrene dimmers (shown in Fig. 1B). It can also be acquired from more common natural sources. [13][14][15][16][17] It was reported that various derivatives of 1,4-benzodioxan show biological activities, [18][19][20] some of which are anticancer agents 21) or new anti-inflammatory compounds.18) The aim of this study is to design a series of hydrazide-Schiff bases with a spectrum of antibactrial applications. In view of the findings mentioned above, we report in this present work the synthesis of a series of 1,4-benzodioxan acylhydrazone derivatives (showed in Fig. 1C) to achieve new potential antibacterial FabH inhibitors. Results and DiscussionChemistry In this study, twenty-one cinnamaldehydeacylhydrazone derivatives were designed and synthesized. The synthesis of compounds A3-9; B3-9 and C3-9 followed the general pathway outlined in Chart 1. All of them were prepared in three steps, which is based on our previous research. with 85% hydrazine monohydrate in ethanol. The synthesis of compounds A3-9, B3-9...

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“…1). They resulted from replacement of the 1,4-benzoxazine core by a 1,4-benzodioxine scaffold [36], a privileged heterocyclic skeleton applied in the design of selective a 1 adrenoceptor antagonists [37], antioxidants [38,39], radical scavenging compounds [40e42], hypolipidemic [43] and antiinflammatory agents [44,45]. In order to explore the significance of chirality and regioisomerism in balancing the activity of the new 1,4-benzodioxine compounds at both targets, and thanks to the commercial availability of both (R)-and (S)-glycidol (required for enantioselective synthesis of the parent 2-substituted benzodioxine cores), we prepared both enantiomers of the benzodioxine 6-and 7-regioisomers and studied the effects of chirality and regioisomerism on binding the resulting potential dual antithrombotic compounds to thrombin and platelet fibrinogen receptor.…”

Section: Introductionmentioning

confidence: 99%

Towards dual antithrombotic compounds – Balancing thrombin inhibitory and fibrinogen GPIIb/IIIa binding inhibitory activities of 2,3-dihydro-1,4-benzodioxine derivatives through regio- and stereoisomerism

Ilić

Ilaš

Chabielska

et al. 2013

European Journal of Medicinal Chemistry

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a b s t r a c tEnantiomers of 2,3-dihydro-1,4-benzodioxine derivatives possessing both thrombin and fibrinogen GPIIb/IIIa binding inhibitory activities were prepared from (R)-and (S)-glycidol as potential dual antithrombotic compounds. The influence of chirality and substitution pattern on thrombin inhibition and on inhibition of fibrinogen binding to GPIIb/IIIa was analyzed. Docking studies were used in an attempt to rationalize the results. The (S)-isomers of both 2,3-dihydro-1,4-benzodioxine regioisomers at positions 6 and 7 were found to be better thrombin inhibitors than the corresponding (R)-enantiomers, whereas we observed that stereochemistry does not display a consistent influence on fibrinogen GPIIb/ IIIa binding inhibitory activity. Compound 11b, the (S)-isomer of the 6-substituted regioisomer, possessed the best balanced dual activity, with K i(thrombin) ¼ 1.67 AE 0.27 mM and IC 50(GPIIb/ IIIa) ¼ 0.665 AE 0.26 mM, raising the hope that merging anticoagulant and platelet antiaggregatory activities in the same molecule could lead to successful multitarget antithrombotic agents.

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Synthesis and biological activity of new anti-inflammatory compounds containing the 1,4-benzodioxine and/or pyrrole system

Cited by 83 publications

References 27 publications

Synthesis and Structure Activity Relationship of Some Indole Derivatives as Potential Anti-inflammatory Agents

Synthesis and Structure Activity Relationship of Some Indole Derivatives as Potential Anti-inflammatory Agents

Synthesis and Antibacterial Activity of Cinnamaldehyde Acylhydrazone with a 1,4-Benzodioxan Fragment as a Novel Class of Potent β-Ketoacyl–Acyl Carrier Protein Synthase III (FabH) Inhibitor

Towards dual antithrombotic compounds – Balancing thrombin inhibitory and fibrinogen GPIIb/IIIa binding inhibitory activities of 2,3-dihydro-1,4-benzodioxine derivatives through regio- and stereoisomerism

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