Synthesis, in vitro and in vivo biological evaluation, COX-1/2 inhibition and molecular docking study of indole-N-acylhydrazone derivatives

Almeida

et al. 2020

IJMS

The compound (E)-2-cyano-3-(1H-indol-3-yl)-N-phenylacrylamide (ICMD-01) was designed and developed based on the structures of clinically relevant drugs indomethacin and paracetamol through the molecular hybridization strategy. This derivative was obtained by an amidation reaction between substituted anilines and ethyl 2-cyanoacetate followed by a Knoevenagel-type condensation reaction with indole aldehyde that resulted in both a viable synthesis and satisfactory yield. In order to assess the immunomodulatory and anti-inflammatory activity, in vitro assays were performed in J774 macrophages, and significant inhibitions (p < 0.05) of the production of nitrite and the production of cytokines (IL-1β and TNFα) in noncytotoxic concentrations were observed. The anti-inflammatory effect was also studied via CFA-induced paw edema in vivo tests and zymosan-induced peritonitis. In the paw edema assay, ICMD01 (50 mg kg−1) showed satisfactory activity, as did the group treated with dexamethasone, reducing edema in 2–6 h. In addition, there was no significant inhibition of PGE2, IL-1β or TNFα in vivo. Moreover, in the peritonitis assay that assesses leukocyte migration, ICMD-01 exhibited promising results. Therefore, these preliminary studies demonstrate this compound to be a strong candidate for an anti-inflammatory drug together with an improved gastrointestinal safety profile when compared to the conventional anti-inflammatory drugs.

Section: In Silico Pharmacokinetic Predictionsmentioning

confidence: 99%

(E)-2-Cyano-3-(1H-Indol-3-yl)-N-Phenylacrylamide, a Hybrid Compound Derived from Indomethacin and Paracetamol: Design, Synthesis and Evaluation of the Anti-Inflammatory Potential

Almeida

et al. 2020

IJMS

“…The COX-1 and COX-2 inhibitory effects of LME and FME were carried out by using spectrophotometric methods [30]. Diclofenac and celecoxib were used positive controls for COX-1 and COX-2, methanol (%1) as blank.…”

Section: Cox-1 and Cox-2 Inhibition Assaymentioning

confidence: 99%

Total phenolic content, cyclooxygenases, ?-glucosidase, acetylcholinesterase, tyrosinase inhibitory and DPPH radical scavenging effects of Cornus sanguinea leaves and fruits

Barut¹,

Şöhretoğlu²

2020

jrp

The aim of the present study was to investigate total phenolic content and biological effects of methanol extracts from Cornus sanguinea L. leaves (LME) and fruits (FME). Total phenolic contents, COX-1/COX-2, αglucosidase, AChE, tyrosinase inhibitory and DPPH radical scavenging effects of both extracts were investigated by using spectrophotometric methods. The total phenolic contents of LME and FME were determined as 191.14 ± 4.84 and 31.51 ± 2.68 mg GAE/g dry weight, respectively. LME inhibited COX-1 enzyme 70.71 ± 1.88% and 79.38 ± 0.92% at 50 and 100 µg/mL. LME had higher COX-1 and COX-2 inhibitory effects than that of FME. LME inhibited αglucosidase stronger than positive control, acarbose. On the other hand, both extracts showed lower AChE inhibition actions compared to positive control, galantamine. Moreover, LME had higher tyrosinase inhibitory effect than FME. Both extracts scavenged DPPH radical in a concentration-dependent manner. Also, LME had stronger scavenging effect than that of FME. To our knowledge, current work is the first report on tyrosinase, AChE, as well as COX-1 inhibitory properties of C. sanguinea. These results suggested that LME of C. sanguinea have a promising potential for the treatment of several disorders but further studies are needed to support the this assumption.

Brazilian Journal of Pain

“…In addition to carrageenan 31 , which is the most used proinflammatory mediator, histamine 32 , dextran 33 , xylene, and serotonin 34 , bradykinin and prostaglandin can be used 35 .…”

Section: Carrageenan-induced Intraplantar Edema 26mentioning

confidence: 99%

In vivo methods for the evaluation of anti-inflammatory and antinoceptive potential

Junior

de²

2019

BACKGROUND AND OBJECTIVES: The constant search for bioactive compounds with anti-inflammatory and antinociceptive activities are of interest to research centers. For the characterization of these activities, trials on guinea pigs are necessary. Therefore, the purpose of this study was to demonstrate some methods to evaluate the anti-inflammatory and antinociceptive potential of natural products. CONTENTS: A stimulus is required to evaluate these activities, and the induction of inflammatory or nociceptive process can be by chemical inducers like formaldehyde, carrageenan, among others, or electronic equipment such as the hot plate. For all assays, the baseline and post-dose measurement of the studied compound is always compared with a control group. The planning of the experiment, as well as its conduct in accordance with well-established protocols, are important tools in the success of the work. The tests presented evaluated the antinociceptive and anti-inflammatory activity as well as the mechanisms involved. CONCLUSION: It was possible to evaluate that the tests present in the literature today meet the researcher's need for the elucidation of the anti-inflammatory and antinociceptive activity of new compounds.