Design and synthesis of ibuprofen-quinoline conjugates as potential anti-inflammatory and analgesic drug candidates

The research on resveratrol (1) has been conducted intensively over a long time due to its proven antioxidant activity and disease-fighting capabilities. Many efforts have also been made to increase these biological effects. In the present study, six new extended aromatic resveratrol analogues containing naphthalene (2) and its bioisosteres quinoline (3 and 4), isoquinoline (5) quinoxaline (6) and quinazoline (7) scaffolds were designed and synthesized using an annulation strategy. The antioxidant and anti-inflammatory activities of these compounds were investigated. All compounds showed better antioxidant activity than resveratrol in ABTS assay. As for the anti-inflammatory test, 5 and 7 exhibited better activity than resveratrol. It is worth noting that nitrogen substitution on the extended aromatic resveratrol analogues has a significant impact on cell viability. Taking the antioxidant activities and NO inhibition activities into consideration, we conclude that isoquinoline analogue 5 may qualify for the further investigation of antioxidant and anti-inflammatory therapy. Furthermore, our study results suggest that in order to improve the biological activity of polyphenolic compounds, extended aromaticity and nitrogen substitution strategy could be a viable method for the design of future drug candidates.

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Design, Synthesis and Pharmacological Evaluation of Novel Antiinflammatory and Analgesic O-Benzyloxime Compounds Derived From Natural Eugenol

Letters in Drug Design & Discovery ◽

10.2174/1570180815666180620145609 ◽

2019 ◽

Vol 16 (10) ◽

pp. 1157-1166

Author(s):

Rodrigo César da Silva ◽

Fabiano Veiga ◽

Fabiana Cardoso Vilela ◽

André Victor Pereira ◽

Thayssa Tavares da Silva Cunha ◽

...

Keyword(s):

Formalin Test ◽

Docking Studies ◽

Paw Edema ◽

Inhibitory Effects ◽

Structural Pattern ◽

Design Synthesis ◽

Drug Candidates ◽

Anti Inflammatory ◽

Analgesic Activities ◽

Cox 1

Background: : A new series of O-benzyloximes derived from eugenol was synthesized and was evaluated for its antinociceptive and anti-inflammatory properties. Methods: : The target compounds were obtained in good global 25-28% yields over 6 steps, which led us to identify compounds (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-(4- (methylthio)benzyloxime (8b), (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-4- bromobenzyloxime (8d) and (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-4- (methylsulfonyl)benzyloxime (8f) as promising bioactive prototypes. Results:: These compounds have significant analgesic and anti-inflammatory effects, as evidenced by formalin-induced mice paw edema and carrageenan-induced mice paw edema tests. In the formalin test, compounds 8b and 8f evidenced both anti-inflammatory and direct analgesic activities and in the carrageenan-induced paw edema, with compounds 8c, 8d, and 8f showing the best inhibitory effects, exceeding the standard drugs indomethacin and celecoxib. Conclusion: : Molecular docking studies have provided additional evidence that the pharmacological profile of these compounds may be related to inhibition of COX enzymes, with slight preference for COX-1. These results led us to identify the new O-benzyloxime ethers 8b, 8d and 8f as orally bioactive prototypes, with a novel structural pattern capable of being explored in further studies aiming at their optimization and development as drug candidates.

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Design and Synthesis of Quinazolinone Derivatives as Anti-inflammatory Agents: Pharmacophore Modeling and 3D QSAR Studies

Medicinal Chemistry ◽

10.2174/1573406409666131128142843 ◽

2014 ◽

Vol 10 (7) ◽

pp. 711-723 ◽

Cited By ~ 4

Author(s):

P. Chaitanya ◽

G. Reddy ◽

G. Varun ◽

L.M. Srikanth ◽

V.V.S.R. Prasad ◽

...

Keyword(s):

3D Qsar ◽

Pharmacophore Modeling ◽

Qsar Studies ◽

Design And Synthesis ◽

Anti Inflammatory ◽

Quinazolinone Derivatives

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Thiophene-Based Compounds with Potential Anti-Inflammatory Activity

Pharmaceuticals ◽

10.3390/ph14070692 ◽

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.

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Diterpenes from Euphorbia myrsinites and Their Anti-inflammatory Property

Planta Medica ◽

10.1055/a-1479-2866 ◽

2021 ◽

Author(s):

Laura Grauso ◽

Bruna de Falco ◽

Giuseppe Lucariello ◽

Raffaele Capasso ◽

Virginia Lanzotti

Keyword(s):

Folk Medicine ◽

Phytochemical Analysis ◽

Spectroscopic Techniques ◽

Significant Activity ◽

Relative Configuration ◽

Drug Candidates ◽

The Usa ◽

Anti Inflammatory ◽

Dose Dependent ◽

Diterpene Alcohol

Abstract Euphorbia myrsinites is one of the oldest spurges described and used in folk medicine. It is characterized by blue-grey stems similar to myrtle, and it is spread in the Mediterranean region, Asia, and the USA. Chemical analysis of E. myrsinites collected in Turkey afforded the isolation of 4 diterpenes based on the so-called myrsinane skeleton being tetraesters of the tetracyclic diterpene alcohol myrsinol. In this study, the phytochemical analysis of this species collected in Italy has been undertaken to afford the isolation of a new atisane diterpene, named myrsatisane, 3 ingenol derivatives, along with the 4 tetraester derivatives previously found. A triterpene compound based on the euphane skeleton has also been isolated. Structural elucidation of the new myrsatisane was based on spectroscopic techniques, including HR-MS and 1- and 2-dimensional NMR experiments. Its relative configuration was determined by NOE correlations, while absolute stereochemistry was obtained by quantum-mechanical DFT studies. While diterpenes with the atisane skeleton are relatively common in Euphorbia species, this is the first report of an atisane diterpene from E. myrsinites. All the isolated terpenes were tested for anti-inflammatory activity on J774A.1 macrophages stimulated with lipopolysaccharide by evaluation of nitrite and pro-inflammatory cytokine Il-1β levels. Among tested compounds, the 3 ingenol diterpenes exhibited a dose-dependent (0.001 – 3 µM) significant activity, thus showing their potential as anti-inflammatory drug candidates.

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Harnessing the medicinal properties of Cussonia barteri Seem. (Araliaceae) in drug development. A review

Herba Polonica ◽

10.2478/hepo-2018-0018 ◽

2018 ◽

Vol 64 (3) ◽

pp. 50-61 ◽

Cited By ~ 1

Author(s):

Ighodaro Igbe ◽

Osaze Edosuyi ◽

Agbonlahor Okhuarobo

Keyword(s):

Drug Development ◽

Antioxidant Activities ◽

Biological Activities ◽

Stem Bark ◽

Deciduous Tree ◽

Drug Candidates ◽

Medicinal Properties ◽

Phytochemical Constituents ◽

Anti Inflammatory ◽

Novel Drug

Summary Cussonia barteri Seem (Araliaceae) is a deciduous tree growing in savannah of Africa. Ethnomedicinally, it is used in Africa as an analgesic, anti-malarial, anti-inflammatory, anti-anaemic, anti-diarhoea, anti-poison, ani-pyschotic and anti-epileptic agent. This review provides a brief summary on the phytochemical screenings, ethnomedicinal and pharmacological applications of various parts of C. barteri. Leaves, stem bark and seed of C. barteri have been shown to be rich in saponins, flavonoids, phenols, sugars and alkaloids. Some of these constituents have been isolated and elucidated from C. barteri. Several compounds isolated from plant include triterpenes, saponins, polyenyne and quinic esters. Phytochemical constituents are also partly responsible for biological activities of C. barteri. Extracts and components isolated from the plant have demonstrated neuropharmacological, anti-larvicidal, anti-microbial, anti-inflammatory and antioxidant activities. Overall, the insights provided by this review reinforce the potential of C. barteri for drug development and create the need for further scientific probe of constituents of the plant with the aim of developing novel drug candidates.

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Peripheral Tramadol in Dentistry: A New Use for an Old Drug

Odovtos - International Journal of Dental Sciences ◽

10.15517/ijds.v0i0.23490 ◽

2016 ◽

Vol 18 (2) ◽

pp. 10

Author(s):

Daniel Chavarría DDS, MSc, PhD ◽

Amaury Pozos DDS, MSc, PhD

Keyword(s):

Adverse Effects ◽

Opioid Receptors ◽

Analgesic Effect ◽

Health Sciences ◽

Analgesic Drug ◽

Orofacial Region ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

New Perspective ◽

Inflammatory Action

Tramadol is a well known central acting analgesic drug, used in a wide variety of treatments within health sciences; including dentistry. Due to its lack of anti-inflammatory action and some adverse effects related mainly to opioid receptors agonism, it is not use as a routine alternative; keeping mainly for patients allergic to non-steroideal anti-inflammatory drugs or as an adjuvant to manage severe odontogenic pain. Since new available evidence supports the possible analgesic effect of this drug when is applied locally in different sites, recent reports have been done to explore the same effect in the orofacial region, especially to improve the local management of odontogenic pain. This new perspective article summarize some of the current efforts develop to explore the peripheral Tramadol in dentistry; “a new use for an old drug”.

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Design and synthesis of novel 1,3,5-triphenyl pyrazolines as potential anti-inflammatory agents through allosteric inhibition of protein kinase Czeta (PKCζ)

MedChemComm ◽

10.1039/c8md00100f ◽

2018 ◽

Vol 9 (6) ◽

pp. 1076-1082 ◽

Cited By ~ 1

Author(s):

Mohammad Abdel-Halim ◽

Ashraf H. Abadi ◽

Matthias Engel

Keyword(s):

Protein Kinase ◽

Mouse Models ◽

Cell Lines ◽

Lead Compound ◽

Allosteric Inhibition ◽

Murine Cell ◽

Design And Synthesis ◽

Anti Inflammatory

A new focused library of PKCζ inhibitors was synthesized, leading to the identification of compound2h. Owing to its improved cellular potency in human and murine cell lines, this new lead compound opens up the possibility to evaluate allosteric PKCζ inhibitors in rat or mouse models.

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