Synthesis of o-(4-fluorobenzoyl) acetaminophen and analgesic testing.
Journal name: World Journal of Pharmaceutical Research
Original article title: Synthesis of o-(4-fluorobenzoyl) acetaminophen and analgesic activity test in mice (mus musculus)
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Ulfa Fikria Putri, Dwita Saraswati, Naili Uswatun Hasanah, Bambang Tri Purwanto, Siswandono
World Journal of Pharmaceutical Research:
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Full text available for: Synthesis of o-(4-fluorobenzoyl) acetaminophen and analgesic activity test in mice (mus musculus)
Source type: An International Peer Reviewed Journal for Pharmaceutical and Medical and Scientific Research
Doi: 10.20959/wjpr201717-10368
Copyright (license): WJPR: All rights reserved
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Summary of article contents:
Introduction
Acetaminophen, a widely used analgesic, poses a risk of hepatotoxicity when consumed in high doses or for prolonged periods. This toxicity arises from its metabolite, NAPQI, which can bind to liver cells and cause damage. To enhance acetaminophen's analgesic properties while minimizing toxicity, researchers synthesized a derivative, O-(4-fluorobenzoyl)acetaminophen, and assessed its analgesic activity in mice (Mus musculus) via the hot plate method. The study aimed to investigate the synthesis of this derivative and evaluate its effectiveness as an analgesic compared to regular acetaminophen.
Increasing Analgesic Activity through Structural Modification
To improve the analgesic effects and safety profile of acetaminophen, the structure was modified through the synthesis of O-(4-fluorobenzoyl)acetaminophen. The synthesis employed a modified Schotten-Baumann reaction, where the hydroxyl group of acetaminophen acted as a nucleophile in a nucleophilic substitution reaction with 4-fluorobenzoyl chloride. This structural modification is expected to enhance the lipophilic properties of the compound, thereby facilitating better receptor interaction and potentially decreasing the likelihood of hepatotoxicity due to the absence of the reactive -OH group.
Purity and Structural Identification Methods
The synthesized derivative was subjected to various analytical techniques to ensure its purity and to confirm the successful structural modification. Purity was assessed using thin layer chromatography (TLC) with different solvent systems, which indicated that the desired compound was formed. The melting point of the synthesized compound was found to be different from that of acetaminophen, suggesting a successful synthesis. Additionally, spectral analyses using UV-Vis, Infrared (IR), and 1H-NMR spectrometry provided further confirmation of the compound's structure, demonstrating the acylation of the hydroxyl group.
Analgesic Activity Testing Results
The study further evaluated the analgesic activity of the synthesized compound using the hot plate method, which assesses the central analgesic effect. Mice were treated with differing dosages of the synthesized compound and regular acetaminophen. Results indicated that O-(4-fluorobenzoyl)acetaminophen exhibited a greater analgesic effect than acetaminophen, with a peak effect occurring later. This suggests that the structural modification not only enhanced the drug's efficacy but also potentially reduced its toxicity profile.
Conclusion
In conclusion, the successful synthesis of O-(4-fluorobenzoyl)acetaminophen has demonstrated significantly greater analgesic activity compared to acetaminophen in vivo. The modification of the acetaminophen structure through acylation not only improved its efficacy but also addressed the concern of hepatic toxicity associated with the parent compound. This research presents O-(4-fluorobenzoyl)acetaminophen as a promising candidate for a new non-steroidal anti-inflammatory drug (NSAID) that could reduce complications related to acetaminophen use. Further investigations are warranted to explore its clinical potential and safety in humans.
FAQ section (important questions/answers):
What is the purpose of synthesizing O-(4-fluorobenzoyl) acetaminophen?
The purpose is to synthesize a derivative of acetaminophen to evaluate its analgesic activity, aiming to enhance its effects while potentially reducing toxicity.
What method was used to synthesize O-(4-fluorobenzoyl) acetaminophen?
The synthesis was performed by acylating acetaminophen with 4-fluorobenzoyl chloride using a modified Schotten-Baumann reaction in a basic solvent.
How was the purity of the synthesized compound verified?
Purity was assessed using Thin Layer Chromatography (TLC) and melting point determination, confirming the desired compound was synthesized with relative purity.
What was the result of the analgesic activity test in mice?
The test showed that O-(4-fluorobenzoyl) acetaminophen had greater analgesic activity than regular acetaminophen when tested using the hot plate method.
What are the potential benefits of O-(4-fluorobenzoyl) acetaminophen?
It is predicted to possess better analgesic properties and lower hepatotoxicity due to the absence of the -OH group, making it a potential alternative NSAID.
What animals were used in the analgesic activity test?
The analgesic activity was tested on white mice (Mus musculus), focusing on their behavioral response to heat stimulus on the hot plate.
Glossary definitions and references:
Scientific and Ayurvedic Glossary list for “Synthesis of o-(4-fluorobenzoyl) acetaminophen and analgesic testing.”. This list explains important keywords that occur in this article and links it to the glossary for a better understanding of that concept in the context of Ayurveda and other topics.
1) Activity:
In the context of pharmacology, 'activity' refers to the effectiveness of a compound in producing a desired physiological effect, such as pain relief. This study measured the analgesic activity of O-(4-fluorobenzoyl)acetaminophen compared to acetaminophen, highlighting the relevance of evaluating a drug's impact on pain management.
2) Animal:
In biomedical research, animals are often used as subjects for testing drugs and evaluating their effects. The study used Mus musculus (mice) to assess the analgesic efficacy of the synthesized compound. Using animals is crucial for understanding how treatments may work in humans.
3) Pain:
'Pain' is a complex sensory experience that signals actual or potential tissue damage. It motivates individuals to seek relief through analgesics. Understanding pain and its mechanisms is vital in developing effective medications like O-(4-fluorobenzoyl)acetaminophen, which aims to provide better pain relief than standard treatments.
4) Study (Studying):
The term 'study' encapsulates the systematic investigation conducted to synthesize O-(4-fluorobenzoyl)acetaminophen and evaluate its analgesic properties. In scientific research, studies are essential for validating hypotheses and exploring new compounds to improve therapeutic interventions.
5) Drug:
A 'drug' is a substance used to diagnose, cure, treat, or prevent disease. In this research, acetaminophen is the reference drug, and the study explores a novel derivative, O-(4-fluorobenzoyl)acetaminophen, to enhance analgesic activity while potentially reducing toxicity.
6) Purity:
'Purity' refers to the extent to which a compound is free from impurities. The study confirmed the purity of synthesized O-(4-fluorobenzoyl)acetaminophen through techniques like thin-layer chromatography and melting point analysis, ensuring its suitability for further testing and efficacy evaluation.
7) Toxicity:
This term describes the degree to which a substance can cause harm or adverse effects. The study investigated the toxicity of O-(4-fluorobenzoyl)acetaminophen in contrast to acetaminophen, aiming to develop a safer alternative analgesic by modifying the existing drug structure.
8) Observation:
'Observation' in scientific research involves monitoring and recording data during experiments. In this study, the latency time in the hot plate test was observed to assess analgesic effectiveness. Observational data are critical for drawing conclusions about a drug's performance.
9) Water:
In the context of this study, 'water' is relevant as a solvent for various reactions and a medium for dissolving compounds. Proper solvent selection is crucial in synthesis processes to ensure efficient reactions and purify the target compound.
10) Hind:
'Hind' typically refers to the back part of the body, particularly in animals. In this study, 'hind' is associated with the hind legs of mice, which were monitored for reflex actions during the pain assessment test, evaluating the effectiveness of the test compound.
11) Pharmacology:
Pharmacology is the branch of medicine concerned with the study of drugs and their effects. This study falls under pharmacology, as it investigates the synthesis and analgesic activity of O-(4-fluorobenzoyl)acetaminophen, contributing to the understanding of pain relief mechanisms and drug design.
12) Calculation:
'Calculation' refers to the mathematical process involved in determining the appropriate dosages for the experiment. In this study, Body Surface Area (BSA) and Human Effective Dose (HED) calculations ensured accurate dosing for the mice, maximizing the reliability of the results.
13) Perception:
'Perception' relates to how sensory experiences like pain are recognized and interpreted by the brain. This study explores how altering drug structure might change pain perception through enhanced pharmacological activity, linking chemical properties to physiological responses.
14) Discussion:
The 'discussion' section of a research study interprets findings, connects results to existing literature, and suggests implications. In this study, the discussion reflects on the significance of the enhanced analgesic activity of O-(4-fluorobenzoyl)acetaminophen and its potential clinical applications.
15) Attacking:
'Attacking' here refers to the nucleophilic action of the phenolic hydroxyl group in acetaminophen during the synthesis of the derivative. This is crucial in organic chemistry, where reactions often involve functional groups 'attacking' electrophiles to form new compounds.
16) Medicine:
Medicine is the field dedicated to diagnosing, treating, and preventing diseases. This study contributes to medicinal chemistry by investigating a derivative of acetaminophen, aiming to develop safer and more effective analgesics for pain management.
17) Relative:
The term 'relative' in this context can denote the comparative assessment between the synthesized compound and acetaminophen regarding effectiveness and safety. Relative evaluations are essential in pharmacology to determine which compounds offer better therapeutic options.
18) Science (Scientific):
'Science' refers to systematic knowledge derived from observation and experimentation. This study employs scientific methods to explore chemical synthesis and evaluate pharmacokinetic properties, contributing to the broader field of pharmaceutical sciences.
19) Surface:
'Surface' may refer to the surface area in pharmacological terms affecting absorption and bioavailability. Surface area calculations can influence how a drug is dosed or how it interacts with biological membranes, directly impacting its effectiveness in pain relief.
20) Amanda (Amamda):
This name appears in the references and is associated with a study on pain definitions. It signifies collaboration in the scientific community, highlighting the importance of influential works that shape contemporary understandings of pain and analgesia.
21) Desire:
'Desire' relates to the motivation behind drug development, reflecting the human need for effective pain relief. The study embodies this desire by seeking to improve analgesic properties while minimizing adverse effects for better therapeutic outcomes.
22) Lamp:
'Lamp' is not directly referenced in the study but may symbolize illumination and learning in scientific research. Metaphorically, it reflects the pursuit of knowledge and understanding in developing effective compounds to address health issues.
23) Salt (Salty):
'Salt' refers to the chemical compounds formed by the combination of acids and bases. In the synthesis process, triethylamine captures HCl to form a salt that facilitates the reaction, showcasing the role of chemical engineering in drug development.
24) Coma:
The term 'coma' denotes a state of profound unconsciousness, which can be a severe consequence of acetaminophen overdose. Understanding the risks of toxicity emphasizes the importance of developing new analgesics with a safer profile through chemical modifications.
Other Science Concepts:
Discover the significance of concepts within the article: ‘Synthesis of o-(4-fluorobenzoyl) acetaminophen and analgesic testing.’. Further sources in the context of Science might help you critically compare this page with similair documents:
Central analgesic activity, Melting point determination, Hot plate method, UV-Vis spectrophotometer, Acetaminophen hepatotoxicity, TLC test.