Synthesis of Acetaminophen Analogues Containing α-Amino Acids and Fatty Acids for Inhibiting Hepatotoxicity

Synthesis ◽  
2019 ◽  
Vol 51 (19) ◽  
pp. 3683-3696
Author(s):  
Seunghee Jung ◽  
Yuya Kawashima ◽  
Takuya Noguchi ◽  
Nobuyuki Imai
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Side Effects ◽  
Lower Incidence ◽  
Reactive Metabolite ◽  
Benzoquinone Imine ◽  
Aniline Derivatives ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Acetaminophen is a popular antipyretic analgesic medicine that has weaker anti-inflammatory properties and lower incidence of side effects than nonsteroidal anti-inflammatory drugs (NSAIDs). However, acetaminophen causes hepatotoxicity due to the reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI). We have obtained acetaminophen analogues in 57–99% yields by using aniline derivatives with protected α-amino acids and fatty acids via the corresponding mixed carbonic carboxylic anhydrides in aqueous MeCN. We have also succeeded in synthesizing AM404 analogues in 76–97% yields, which are expected to be promising candidates for reducing hepatotoxicity.

scholarly journals Phytochemical research and anti-inflammatory activity of the dry extracts from northern highbush blueberry leaves

2021 ◽  
pp. 40-48
Author(s):  
Oleksandr Stremoukhov ◽  
Oleh Koshovyi ◽  
Mykola Komisarenko ◽  
Igor Kireyev ◽  
Andriy Gudzenko ◽  
...  
Keyword(s):  
Amino Acids ◽  
Phenolic Compounds ◽  
Side Effects ◽  
New Drugs ◽  
Inflammatory Activity ◽  
Highbush Blueberry ◽  
Northern Highbush Blueberry ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Blueberry Leaves

All over the world, non-steroidal anti-inflammatory drugs (NSAIDs) are taken annually by about three hundred million people and this figure is constantly increasing. At the same time, NSAIDs are also one of the most common causes of side effects of drug therapy. The development and implementation of new anti-inflammatory drugs, including those of plant origin, with minimal side effects is an urgent task of modern pharmaceutical science. Vaccinium corymbosum L. (family Ericaceae), which is gaining more and more popularity among berry crops and is successfully cultivated in Ukraine, is promising in this direction for research. The aim: phytochemical analysis of dry extracts from blueberry leaves to establish the possibility of creating new drugs with anti-inflammatory activity. Materials and methods. The objects of the study were dry extracts of northern highbush blueberry leaves. The content of amino acids and phenolic compounds was determined by HPLC and spectrophotometry. The prototypal activity was studied in vivo and in vitro. Research results. 4 dry extracts were obtained from northern highbush blueberry leaves. In the extracts obtained by HPLC, 7 amino acids were identified, including 3 essential ones: arginine, histidine, and phenylalanine. As a result of the HPLC study, 7 phenolic compounds were identified in extracts from the leaves of northern highbush blueberry: 5 flavonoids - rutin, quercetin-3-O-glucoside, kaempferol-3-O-glucoside, quercetin and kaempferol and 2 hydroxycinnamic acids, chlorogenic and caffeic acid. For the first time, the anti-inflammatory effect of extracts from blueberry leaves was investigated. It was revealed that extract 1 at a dose of 50 mg/kg and extract 4 modified with arginine at a dose of 25 mg/kg have the highest anti-inflammatory activity. Conclusions. The results of the conducted studies indicate that extracts from the leaves of northern highbush blueberry in terms of the content of biologically active substances are promising sources for the creation of new drugs and dietary supplements with anti-inflammatory activity

Risks of Cardiovascular Disease and Beyond in Prescription of Nonsteroidal Anti-Inflammatory Drugs

2019 ◽  
Vol 25 (1) ◽  
pp. 3-6 ◽  
Author(s):  
Manas A. Rane ◽  
Alexander Gitin ◽  
Benjamin Fiedler ◽  
Lawrence Fiedler ◽  
Charles H. Hennekens
Keyword(s):  
Cardiovascular Disease ◽  
Side Effects ◽  
Health Care Providers ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Care Providers ◽  
Relieve Pain ◽  
Gastrointestinal Side Effects ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) include aspirin, naproxen, diclofenac, and ibuprofen, as well as selective cyclooxygenase 2 inhibitors such as celecoxib. Their use is common, as well as their side effects which cause 100 000 hospitalizations and 17 000 deaths annually. Recently, the US Food and Drug Administration strengthened its warning about the risks of cardiovascular disease (CVD) attributed to nonaspirin NSAIDs. Methods: When the sample size is large, randomization provides control of confounding not possible to achieve with any observational study. Further, observational studies and, especially, claims data have inherent confounding by indication larger than the small to moderate effects being sought. Results: While trials are necessary, they must be of sufficient size and duration and achieve high compliance and follow-up. Until then, clinicians should remain uncertain about benefits and risks of these drugs. Conclusions: Since the totality of evidence remains incomplete, health-care providers should consider all these aforementioned benefits and risks, both CVD and beyond, in deciding whether and, if so, which, NSAID to prescribe. The factors in the decision of whether and, if so, which NSAID to prescribe for relief of pain from inflammatory arthritis should not be limited to risks of CVD or gastrointestinal side effects but should also include potential benefits including improvements in overall quality of life resulting from decreases in pain or impairment from musculoskeletal pain syndromes. The judicious individual clinical decision-making about the prescription of NSAIDs to relieve pain based on all these considerations has the potential to do much more good than harm.

The role of celecoxib as a potential inhibitor in the treatment of inflammatory diseases - a review

2021 ◽  
Vol 28 ◽  
Author(s):  
Josiane Viana Cruz ◽  
Joaquín María Campos Rosa ◽  
Njogu Mark Kimani ◽  
Silvana Giuliatti ◽  
Cleydson Breno Rodrigues dos Santos
Keyword(s):  
Side Effects ◽  
Inflammatory Diseases ◽  
Structural Basis ◽  
Potential Inhibitor ◽  
Cyclooxygenase 1 ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors

: This article presents a simplified view of celecoxib as a potential inhibitor in the treatment of inflammatory diseases. The enzyme cyclooxygenase (COX) has, predominantly, two isoforms called cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2). The former plays a constitutive role that is related to homeostatic effects in renal and platelets, while the latter is mainly responsible for induction of inflammatory effects. Since COX-2 plays an important role in the pathogenesis of inflammatory diseases, it has been signaled as a target for the planning of anti-inflammatory intermediates. Many inhibitors developed and planned for COX-2 inhibition have presented side effects to humans, mainly in the gastrointestinal and/or cardiovascular tract. Therefore, it is necessary to design new potential COX-2 inhibitors, which are relatively safe and without side effects. To this end, of the generation of non-steroidal anti-inflammatory drugs from “coxibs”, celecoxib is the only potent selective COX-2 inhibitor that is still commercially available. Thus, the compound celecoxib became a commercial prototype inhibitor for the development of anti-inflammatory agents for COX-2 enzyme. In this review, we provide highlights where such inhibition should provide a structural basis for the design of promising new non-steroidal anti-inflammatory drugs (NSAIDs) which act as COX-2 inhibitors with lesser side effects on the human body.

Reducing pain in certain forms of obstetric pathology: nonsteroidal anti-inflammatory drugs (Сlinical lecture)

2017 ◽  
pp. 9-14
Author(s):  
L. Nazarenko ◽  
Keyword(s):  
Preterm Birth ◽  
Side Effects ◽  
Key Words ◽  
Clinical Efficacy ◽  
Premature Birth ◽  
Pain Syndrome ◽  
Inflammatory Drug ◽  
Threatened Abortion ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

The article discusses the pathogenetic basis for the use of non-steroidal anti-inflammatory drugs (NSPVP) in obstetric practice for the treatment of pain syndrome in women with threatened abortion and pathological preliminary period. Provided with modern views on the mechanisms of analgesic clinical efficacy, side effects NSPVP. Provides information about the place of NSPVP during pregnancy, the risks to the fetus, the positive aspects in the conduct of women at risk of preterm birth, the pathological preliminary period. Key words: nonsteroidal anti-inflammatory drug, pain, premature birth, preliminary period.

Comparative analysis of neurological recovery and adverse effects in chondrodystrophic dogs with thoracolumbar intervertebral disc herniation treated with methylprednisolone versus non-steroidal anti-inflammatory drugs

2021 ◽  
Author(s):  
William McCartney ◽  
Ciprian Andrei Ober ◽  
Maria Benito
Keyword(s):  
Treatment Group ◽  
Side Effects ◽  
Intervertebral Disc ◽  
Disc Herniation ◽  
Sodium Succinate ◽  
Neurological Recovery ◽  
Intervertebral Disc Herniation ◽  
Cord Injury ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Abstract Thoracolumbar intervertebral disc herniation is a common neurologic disease presented to the small-animal practitioner. The use of methylprednisolone sodium succinate (MPSS) as an adjunct to surgical decompression in cases of acute spinal cord injury following intervertebral disc extrusion is controversial. A prospective study was undertaken to compare the preoperative use of MPSS and non-steroidal anti-inflammatory drugs (NSAIDs) in 40 chondrodystrophic dogs presenting with similar signs and undergoing spinal decompressive surgery. Twenty dogs received MPSS and 20 had NSAIDs administered preoperatively. Dogs were administered with either MPSS intravenously 20 minutes before surgery (30 mg/kg) or NSAID (meloxicam 0.2mg/kg or carprofen 4 mg/kg) subcutaneously 20 minutes before surgery. Dogs were evaluated by neurologic examination of gait 24 hours postoperatively, at time of discharge and then at 8 weeks. The neurological recovery were similar in both groups, but the frequency of side effects such as vomiting (MPSS group: 90% versus NSAIDs group: 55%), and anorexia within the first three days (present in all 20 dogs pretreated with MPSS) was significantly different, with complications being more prevalent in the MPSS group. Side effects were significantly more evident with MPSS treatment group –including vomiting and anorexia during the first 3 days after surgery– than with NSAID treatment group, with a neurological recovery similar in both groups.

scholarly journals The conjugation of nonsteroidal anti-inflammatory drugs (NSAID) to small peptides for generating multifunctional supramolecular nanofibers/hydrogels

2013 ◽  
Vol 9 ◽  
pp. 908-917 ◽  
Author(s):  
Jiayang Li ◽  
Yi Kuang ◽  
Junfeng Shi ◽  
Yuan Gao ◽  
Jie Zhou ◽  
...  
Keyword(s):  
Amino Acids ◽  
Critical Concentration ◽  
Therapeutic Agents ◽  
Multiple Roles ◽  
Small Peptides ◽  
Covalent Linkage ◽  
Physiological Conditions ◽  
Racemic Ibuprofen ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Here we report supramolecular hydrogelators made of nonsteroidal anti-inflammatory drugs (NSAID) and small peptides. The covalent linkage of Phe–Phe and NSAIDs results in conjugates that self-assemble in water to form molecular nanofibers as the matrices of hydrogels. When the NSAID is naproxen (1), the resultant hydrogelator 1a forms a hydrogel at a critical concentration (cgc) of 0.2 wt % at pH 7.0. Hydrogelator 1a, also acting as a general motif, enables enzymatic hydrogelation in which the precursor turns into a hydrogelator upon hydrolysis catalyzed by a phosphatase at physiological conditions. The conjugates of Phe–Phe with other NSAIDs, such as (R)-flurbiprofen (2), racemic flurbiprofen (3), and racemic ibuprofen (4), are able to form molecular hydrogels, except in the case of aspirin (5). After the conjugation with the small peptides, NSAIDs exhibit improved selectivity to their targets. In addition, the peptides made of D-amino acids help preserve the activities of NSAIDs. Besides demonstrating that common NSAIDs are excellent candidates to promote aromatic–aromatic interaction in water to form hydrogels, this work contributes to the development of functional molecules that have dual or multiple roles and ultimately may lead to new molecular hydrogels of therapeutic agents for topical use.

Towards developing new strategies to reduce the adverse side-effects of nonsteroidal anti-inflammatory drugs

2011 ◽  
Vol 16 (1) ◽  
pp. 25-29 ◽  
Author(s):  
Noritaka Kawada ◽  
Toshiki Moriyama ◽  
Harumi Kitamura ◽  
Ryohei Yamamoto ◽  
Yoshiyuki Furumatsu ◽  
...  
Keyword(s):  
Side Effects ◽  
Adverse Side Effects ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
New Strategies
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