Evaluation of anti-inflammatory activity and molecular docking study of new aza-bicyclic isoxazoline acylhydrazone derivatives

Mota, Fernanda Virgínia Barreto; Neta, Marlene Saraiva de Araújo; Franco, Eryvelton de Souza; Bastos, Isla Vanessa Gomes Alves; Araújo, Larissa Cardoso Correia da; Silva, Sandra Cabral da; Oliveira, Tatiane Bezerra de; Souza, Eduarda Karynne; Almeida, Valderes Moraes de; Ximenes, Rafael Matos; Maia, Maria Bernadete de Sousa; Mendonça, Francisco Jaime Bezerra; Marchand, Pascal; Faria, Antônio Rodolfo de; Silva, Teresinha Gonçalves da

doi:10.1039/c9md00276f

Cited by 19 publications

(11 citation statements)

References 67 publications

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“…The most common anti-inflammatory cytokines are interleukins IL-4, IL-10, IL-13, and TGFβ (transforming growth factor). The most common proinflammatory cytokines are tumor necrosis factor (TNF), and interleukins IL-1, IL-2, IL-6 and IL-7 [ 5 , 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Thiophene-Based Compounds with Potential Anti-Inflammatory Activity

et al. 2021

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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.

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Section: Introductionmentioning

confidence: 99%

Thiophene-Based Compounds with Potential Anti-Inflammatory Activity

et al. 2021

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“…The Ximenes research group investigated the anti‐inflammatory effects of isoxazoline acylhydrazone ( 16 , 17 ) and interestingly, they were found to be potent inhibitors of the histamine H1 receptor. Furthermore, monitoring compounds 16 and 17 showed a substantial decrease in the production of cytokine levels (TNF‐α and IL‐1β) with 271.60 and 305.88 pg mL −1 in comparison with reference drug indomethacin (TNF‐α=425.17 pg mL −1 ; IL‐1β=564.06 pg mL −1 ) [89] . Park et al.…”

Section: Pharmacological Profile Of Isoxazoline Derivativesmentioning

confidence: 96%

2‐Isoxazolines: A Synthetic and Medicinal Overview

Kumar

Shankar

2020

ChemMedChem

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Isoxazolines are nitrogen‐ and oxygen‐containing five‐membered heterocyclic scaffolds with extensive biological activities. This framework can be readily obtained in good to excellent yields through 1,3‐dipolar cycloaddition between nitrones with alkynes or allenes, aryl/alkyl halides, alkynes, and oxaziridines under mild conditions. This scaffold has been an emerging area of interest for many researchers given their wide range of bioactivities. Herein we review synthetic strategies toward isoxazolines and the role these efforts have had in enhancing the biological activity of natural products and synthetic compounds such as antitubercular agents, COX‐1 inhibitors, COX‐2 inhibitors (e. g., valdecoxib), nicotinic receptor modulators, and MIF inhibitors. With a focus on efforts from 2010 onward, this review provides in‐depth coverage of the design and biological evaluation of isoxazoline systems and their impact on various pathologies.

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“…Indolecarboxamides were reported to form hydrogen bonds with N443 ECL3 , R176 ECL2 , and I 6.58 [ 65 ] while alkyl/aryl piperidyl indole formed electrostatic interactions with conserved Y 6.51 residue [ 69 ]. Several other compounds have been docked to the H 1 R structure such as aminomethylenepyrimidine-2,4,6-triones, N 1 -alkyltheobromine, N-methylanthranilates, azabicyclic isoxazoline acylhydrazones, substituted tetrazole-incorporated quinoline derivative, synthesized rupatadine and desloratadine analogues [ 70 , 73 , 76 , 105 ]. Elbayaa [ 70 ] designed a series of substituted aminomethylenepyrimidine-2,4,6-trione derivatives generated from a four-featured pharmacophore model with an aromatic or π-ring system, hydrophobic group, a H-bond donor and a H-bond acceptor group derived from five H 1 R antagonists and validated this model using six other H 1 R antagonists.…”

Section: Hr-targeted Ligands and Receptor Binding Site Of Inactivementioning

confidence: 99%

Molecular Modeling of Histamine Receptors—Recent Advances in Drug Discovery

Mehta

Filipek

2021

Molecules

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The recent developments of fast reliable docking, virtual screening and other algorithms gave rise to discovery of many novel ligands of histamine receptors that could be used for treatment of allergic inflammatory disorders, central nervous system pathologies, pain, cancer and obesity. Furthermore, the pharmacological profiles of ligands clearly indicate that these receptors may be considered as targets not only for selective but also for multi-target drugs that could be used for treatment of complex disorders such as Alzheimer’s disease. Therefore, analysis of protein-ligand recognition in the binding site of histamine receptors and also other molecular targets has become a valuable tool in drug design toolkit. This review covers the period 2014–2020 in the field of theoretical investigations of histamine receptors mostly based on molecular modeling as well as the experimental characterization of novel ligands of these receptors.

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Evaluation of anti-inflammatory activity and molecular docking study of new aza-bicyclic isoxazoline acylhydrazone derivatives

Abstract: The aim of this study was to investigate the anti-inflammatory effects of two new isoxazoline-acylhydrazone derivatives.

Cited by 19 publications

References 67 publications

Thiophene-Based Compounds with Potential Anti-Inflammatory Activity

Thiophene-Based Compounds with Potential Anti-Inflammatory Activity

2‐Isoxazolines: A Synthetic and Medicinal Overview

Molecular Modeling of Histamine Receptors—Recent Advances in Drug Discovery

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