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.

scholarly journals Selective Recognition of Amino Acids and Peptides by Small Supramolecular Receptors

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 106
Author(s):  
Joana N. Martins ◽  
João Carlos Lima ◽  
Nuno Basílio
Keyword(s):  
Amino Acids ◽  
Selective Recognition ◽  
Great Promise ◽  
Macrocyclic Compounds ◽  
Synthetic Receptors ◽  
Small Peptides ◽  
Molecular Imprinted Polymers ◽  
Polymeric Systems ◽  
Physiological Conditions ◽  
Level Information

To this day, the recognition and high affinity binding of biomolecules in water by synthetic receptors remains challenging, while the necessity for systems for their sensing, transport and modulation persists. This problematic is prevalent for the recognition of peptides, which not only have key roles in many biochemical pathways, as well as having pharmacological and biotechnological applications, but also frequently serve as models for the study of proteins. Taking inspiration in nature and on the interactions that occur between several receptors and peptide sequences, many researchers have developed and applied a variety of different synthetic receptors, as is the case of macrocyclic compounds, molecular imprinted polymers, organometallic cages, among others, to bind amino acids, small peptides and proteins. In this critical review, we present and discuss selected examples of synthetic receptors for amino acids and peptides, with a greater focus on supramolecular receptors, which show great promise for the selective recognition of these biomolecules in physiological conditions. We decided to focus preferentially on small synthetic receptors (leaving out of this review high molecular weight polymeric systems) for which more detailed and accurate molecular level information regarding the main structural and thermodynamic features of the receptor biomolecule assemblies is available.

Green Efficient Synthesis of Oxadiazole Derivatives as Analgesic and Antiinflammatory Agents

2020 ◽  
Vol 7 (2) ◽  
pp. 163-178
Author(s):  
Biswa M. Sahoo ◽  
Bera Venkata V. Ravi Kumar ◽  
Bimal K. Banik ◽  
Preetismita Borah
Keyword(s):  
Therapeutic Agents ◽  
Gastric Ulcers ◽  
Efficient Synthesis ◽  
Significant Side Effect ◽  
Major Class ◽  
Oxadiazole Derivatives ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
By Products ◽  
Alternative Drugs

Non-steroidal anti-inflammatory drugs (NSAIDs) act as a major class of therapeutic agents. The biological activity of NSAIDs is due to the suppression of prostaglandin biosynthesis by inhibiting cyclooxygenase (COX) enzyme. COX is an endogenous enzyme, which catalyzes the conversion of arachidonic acid into prostaglandins. But the significant side effect by NSAIDs is the formation of gastric ulcers, irritation and GI bleeding. Therefore, alternative drugs that can overcome these limitations are necessary. Towards the goal, oxadiazole derivatives are designed and synthesized following a green chemistry approach. This method helps to reduce environmental pollution and the formation of by-products so that the yield of products is increased in less reaction time. It is observed that the anti- inflammatory activity of oxadiazoles is based on dual mechanisms, such as the inhibition of both COX and LOX (lipoxygenase) enzyme thereby reducing gastric ulceration. On this basis, research is carried out to develop efficient anti-inflammatory agents with minimal side effects by incorporating the oxadiazole moiety.

scholarly journals Xanthones, A Promising Anti-Inflammatory Scaffold: Structure, Activity, and Drug Likeness Analysis

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 598 ◽  
Author(s):  
Zheling Feng ◽  
Xiuqiang Lu ◽  
Lishe Gan ◽  
Qingwen Zhang ◽  
Ligen Lin
Keyword(s):  
Therapeutic Agents ◽  
Therapeutic Approaches ◽  
Cell Dysfunction ◽  
Limited Effectiveness ◽  
Multiple Stimulus ◽  
Scaffold Structure ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Inflammation is the body’s self-protective response to multiple stimulus, from external harmful substances to internal danger signals released after trauma or cell dysfunction. Many diseases are considered to be related to inflammation, such as cancer, metabolic disorders, aging, and neurodegenerative diseases. Current therapeutic approaches include mainly non-steroidal anti-inflammatory drugs and glucocorticoids, which are generally of limited effectiveness and severe side-effects. Thus, it is urgent to develop novel effective anti-inflammatory therapeutic agents. Xanthones, a unique scaffold with a 9H-Xanthen-9-one core structure, widely exist in natural sources. Till now, over 250 xanthones were isolated and identified in plants from the families Gentianaceae and Hypericaceae. Many xanthones have been disclosed with anti-inflammatory properties on different models, either in vitro or in vivo. Herein, we provide a comprehensive and up-to-date review of xanthones with anti-inflammatory properties, and analyzed their drug likeness, which might be potential therapeutic agents to fight against inflammation-related diseases.

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

Reversible Sensorineural Hearing Loss after Renal Transplant Immunosuppression with OKT3 (MUROMONAB-CD3)

1997 ◽  
Vol 106 (8) ◽  
pp. 640-642 ◽  
Author(s):  
Christopher J. Hartnick ◽  
Alan F. Cohen ◽  
Richard V. Smith
Keyword(s):  
Monoclonal Antibody ◽  
Hearing Loss ◽  
Renal Transplant ◽  
Sensorineural Hearing Loss ◽  
Therapeutic Agents ◽  
Sensorineural Hearing ◽  
Murine Monoclonal Antibody ◽  
Renal Transplants ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Reversible and irreversible ototoxicity has been documented following the administration of various therapeutic agents. Reversible hearing loss is a known complication following the administration of quinine, salicylates and other nonsteroidal anti-inflammatory drugs, and erythromycin. We report a case of reversible hearing loss following OKT3 (murine monoclonal antibody CD3) administration. OKT3, a monoclonal antibody used as an immunosuppressant following cadaveric renal transplants, was associated with a transient sensorineural hearing loss that reversed following discontinuation of OKT3.

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 The Discovery of Synthetic Proteolytic Peptide

2018 ◽  
Author(s):  
Rina Nakamura ◽  
Motomi Konishi ◽  
Masanari Taniguchi ◽  
Yusuke Hatakawa ◽  
Toshifumi Akizawa
Keyword(s):  
Amino Acids ◽  
Serine Protease ◽  
Proteolytic Activity ◽  
Synthetic Peptide ◽  
Synthetic Peptides ◽  
Serine Protease Inhibitor ◽  
Small Peptides ◽  
Physiological Conditions ◽  
Proteolytic Activities ◽  
Catalytic Peptides

After screening nearly 1000 synthetic peptides, a synthetic peptide termed JAL-AK22 (KYEGHWYPEKPYKGSGFRCIHI) derived from the BoxA domain in Tob1 protein was found to activate both unfolded and folded proMMP-7. In addition, JAL-AK22 showed auto-proteolytic activity. Interestingly, the smaller derivative of JAL-AK22 termed JAL-TA9 (YKGSGFRMI) also possessed auto-proteolytic activity and cleaved 2 fragment peptides (MMP18-33 and MMP18-40) derived from the prodomain of proMMP-7 under physiological conditions. These proteolytic activities were inhibited by AEBSF, a serine protease inhibitor. Our results demonstrate that a small synthetic peptide consisting of only 9 amino acids has serine protease-like activity and activates proMMP-7 by cleaving the prodomain region. We thus propose calling small peptides possessing with protease-like activity Catalytides (catalytic peptides). We expect that our findings will stimulate the development of novel Catalytides and related applications.

scholarly journals The Discovery of Synthetic Proteolytic Peptide

2018 ◽  
Author(s):  
Rina Nakamura ◽  
Aya Kojima ◽  
Motomi Konishi ◽  
Masanari Taniguchi ◽  
Yusuke Hatakawa ◽  
...  
Keyword(s):  
Amino Acids ◽  
Serine Protease ◽  
Proteolytic Activity ◽  
Synthetic Peptide ◽  
Synthetic Peptides ◽  
Serine Protease Inhibitor ◽  
Small Peptides ◽  
Physiological Conditions ◽  
Proteolytic Activities ◽  
Catalytic Peptides

After screening nearly 1000 synthetic peptides, a synthetic peptide termed JAL-AK22 (KYEGHWYPEKPYKGSGFRCIHI) derived from the BoxA domain in Tob1 protein was found to activate both unfolded and folded proMMP-7. In addition, JAL-AK22 showed auto-proteolytic activity. Interestingly, the smaller derivative of JAL-AK22 termed JAL-TA9 (YKGSGFRMI) also possessed auto-proteolytic activity and cleaved 2 fragment peptides (MMP18-33 and MMP18-40) derived from the prodomain of proMMP-7 under physiological conditions. These proteolytic activities were inhibited by AEBSF, a serine protease inhibitor. Our results demonstrate that a small synthetic peptide consisting of only 9 amino acids has serine protease-like activity and activates proMMP-7 by cleaving the prodomain region. We thus propose calling small peptides possessing with protease-like activity Catalytides (catalytic peptides). We expect that our findings will stimulate the development of novel Catalytides and related applications.

Sign in / Sign up

Export Citation Format

Share Document