A Convenient Synthesis, Reactions and Biological Activities of Some Novel Thieno[3,2-e]pyrazolo[3,4-b]pyrazine Compounds as Anti-microbial and Antiinflammatory Agents

2018 ◽  
Vol 15 (6) ◽  
pp. 863-871 ◽  
Author(s):  
Remon M. Zaki ◽  
Remon M. Zaki ◽  
Adel M. Kamal El-Dean ◽  
Adel M. Kamal El-Dean ◽  
Shaban M. Radwan ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Biological Activities ◽  
Ring Closure ◽  
Inflammatory Activity ◽  
Activity Data ◽  
E Coli ◽  
Chemical Structures ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
High Antifungal Activity

Aim and Objective: We reported in this manuscript, synthesis of novel pyrazolopyrazinothienopyrimidines. The o-amino-thienopyrazolopyrazine-carbonitrile 4 was used as a versatile precursor for synthesis of new heterocyclic compounds. Due to development of resistance to the current antimicrobial therapy and non-steroidal anti-inflammatory drugs (NSAIDs), continues research for more effective agents is interesting. Hence, the suspected promising biological activities of pyrazolopyrazine compounds persuaded us to study the anti-microbial and anti-inflammatory activities in comparison with standard drugs. Materials and Methods: The chemical structures of the newly synthesized compounds were confirmed by elemental and spectral analyses. Activities of the synthesized compounds against a number of Gram-negative and Gram-positive bacterial strains were investigated. The fungal strains were obtained from some cases of human dermatophytosis. The antimicrobial activities were determined according to the Kwon-Chung and Bennett method. Anti-inflammatory activity was evaluated using carrageenan induced paw edema method. Results: The antibacterial screening of the synthesized compounds represented that the o-amino-carbonitrile 4 and triazepinone 11 have the highest activity towards E. coli & S. aureus and S. pneumonia. The amino-imino 6 was very effective against E. coli. Ring closure of 6 to triazolopyrimidine 7 increases the antibacterial activity against E. coli & K. pneumonia, their inhibition zones were higher than ciprofloxacin. Also, the triazolopyrimidines 7 and 10 exhibited high antifungal activity against all tested strains. Compounds 6 and 11 revealed high antifungal activity against S. racemosum and T. rubrum. The anti-inflammatory activity data indicated that all the tested compounds 4, 6, 7, 10 & 11 revealed the highest anti-inflammatory effect after 4 hrs. of carrageenan injection. Conclusion: we found that most of the examined novel thieno- pyrazolopyrazine compounds exhibited promising antibacterial, antifungal and anti-inflammatory activities which can be used as potential antibacterial, antifungal and anti-inflammatory drugs.

Design, Synthesis, Characterization and in silico molecular docking studies and in vivo anti-inflammatory Activity of Pyrazoline clubbed Thiazolinone Derivatives

2020 ◽  
Vol 17 ◽  
Author(s):  
Deepak Kumar Singh ◽  
Mayank Kulshreshtha ◽  
Yogesh Kumar ◽  
Pooja A Chawla ◽  
Akash Ved ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Biological Activities ◽  
Inflammatory Activity ◽  
Standard Drug ◽  
Docking Score ◽  
Chemical Structures ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Background: The pyrazolines give the reactions of aliphatic derivatives, resembling unsaturated compounds in their behavior towards permanganate and nascent hydrogen. This nucleus has been associated with various biological activities including inflammatory. Thiazolinone is a heterocyclic compound that contains both sulfur and nitrogen atom with a carbonyl group in their structure.Thiazolinone and their derivatives have attracted continuing interest because of their various biological activities, such as anti-inflammatory, antimicrobial, anti-proliferative, antiviral, anticonvulsant etc. The aim of the research was to club pyrazoline nucleus with thiazolinone in order to have significantanti-inflammatory activity. The synthesized compounds were chemically characterized for the establishment of their chemical structures and to evaluate as anti-inflammatory agent. Method: In the present work, eight derivatives of substituted pyrazoline (PT1-PT8) were synthesized by a three step reaction.The compounds were subjected to spectral analysis by Infrared, Mass and Nuclear magnetic resonance spectroscopy and elemental analysis data. All the synthesized were evaluated for their in vivo anti-inflammatory activity. The synthesized derivatives were evaluated for their affinity towards target COX-1 and COX-2, using indomethacin as the reference compound molecular docking visualization through AutoDock Vina. Results: Compounds PT-1, PT-3, PT-4 and PT-8 exhibited significant anti-inflammatory activity at 3rd hour being 50.7%, 54.3%, 52.3% and 57% respectively closer to that of the standard drug indomethacin (61.9%).From selected anti-inflammatory targets, the synthesized derivatives exhibited better interaction with COX-1 and COX-2 receptor, where indomethacin showed docking score of -6.5 kJ/mol, compound PT-1 exhibited highest docking score of -9.1 kJ/mol for COX-1 and compound PT-8 having docking score of 9.4 kJ/mol for COX-2. Conclusion: It was concluded that synthesized derivatives have more interaction with COX-2 receptors in comparison to the COX-1 receptors because the docking score with COX-2 receptors were very good. It is concluded that the synthesized derivatives (PT-1 to PT-8) are potent COX-2 inhibitors.

scholarly journals Biosynthesis of resveratrol derivatives and evaluation of their anti-inflammatory activity

2021 ◽  
Vol 64 (1) ◽  
Author(s):  
Yoojin Chong ◽  
Hye Lim Lee ◽  
Jihyeon Song ◽  
Youngshim Lee ◽  
Bong-Gyu Kim ◽  
...  
Keyword(s):  
Biological Activities ◽  
Stilbene Synthase ◽  
Inflammatory Activity ◽  
E Coli ◽  
Prephenate Dehydrogenase ◽  
Coa Ligase ◽  
Final Yield ◽  
Resveratrol Derivatives ◽  
Anti Inflammatory ◽  
Tyrosine Biosynthesis

AbstractResveratrol is a typical plant phenolic compound whose derivatives are synthesized through hydroxylation, O-methylation, prenylation, and oligomerization. Resveratrol and its derivatives exhibit anti-neurodegenerative, anti-rheumatoid, and anti-inflammatory effects. Owing to the diverse biological activities of these compounds and their importance in human health, this study attempted to synthesize five resveratrol derivatives (isorhapontigenin, pterostilbene, 4-methoxyresveratrol, piceatannol, and rhapontigenin) using Escherichia coli. Two-culture system was used to improve the final yield of resveratrol derivatives. Resveratrol was synthesized in the first E. coli cell that harbored genes for resveratrol biosynthesis including TAL (tyrosine ammonia lyase), 4CL (4-coumaroyl CoA ligase), STS (stilbene synthase) and genes for tyrosine biosynthesis such as aroG (deoxyphosphoheptonate aldolase) and tyrA (prephenate dehydrogenase). Thereafter, culture filtrate from the first cell was used for the modification reaction carried out using the second E. coli harboring hydroxylase and/or O-methyltransferase. Approximately, 89.8 mg/L of resveratrol was synthesized and using the same, five derivatives were prepared with a conversion rate of 88.2% to 22.9%. Using these synthesized resveratrol derivatives, we evaluated their anti-inflammatory activity. 4-Methoxyresveratrol, pterostilbene and isorhapontigenin showed the anti-inflammatory effects without any toxicity. In addition, pterostilbene exhibited the enhanced anti-inflammatory effects for macrophages compared to resveratrol.

scholarly journals New Eunicellin-Type Diterpenes from the Panamanian Octocoral Briareum asbestinum

Marine Drugs ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 84 ◽  
Author(s):  
Marcelino Gutiérrez ◽  
Ricardo Santamaría ◽  
José Félix Gómez-Reyes ◽  
Héctor M. Guzmán ◽  
Javier Ávila-Román ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Biological Activities ◽  
Chemical Study ◽  
Inflammatory Activity ◽  
Bocas Del Toro ◽  
Chemical Structures ◽  
Wide Range ◽  
Marine Compounds ◽  
Anti Inflammatory ◽  
New Compounds

Gorgonian octocorals are considered a prolific source of secondary metabolites with a wide range of biological activities, including anti-inflammatory activity. In particular, the genus Briareum is known for producing a wealth of diterpenes with complex chemical structures. The chemical study of the methanolic extract of Briareum asbestinum collected in Bocas del Toro, on the Caribbean side of Panama, led to the isolation of three new eunicellin-type diterpenes: briarellin T (1), asbestinin 27 (2), asbestinin 28 (3) and the previously described asbestinin 17 (4). The structures of the new compounds were determined by extensive NMR analyses and HRMS. Anti-inflammatory activity assays showed a significant reduction of the pro-inflammatory cytokines TNF-α, IL-6, IL-1β and IL-8 as well as a downregulation of COX-2 expression in LPS-stimulated THP-1 macrophages. These findings support the potential use of these marine compounds as therapeutic agents in the treatment of inflammatory diseases.

scholarly journals Sesquiterpenes from Essential Oils and Anti-Inflammatory Activity

2015 ◽  
Vol 10 (10) ◽  
pp. 1934578X1501001 ◽  
Author(s):  
Rita de Cássia Da Silveira e Sá ◽  
Luciana Nalone Andrade ◽  
Damião Pergentino De Sousa
Keyword(s):  
Side Effects ◽  
Essential Oil ◽  
Therapeutic Potential ◽  
Relevant Information ◽  
Mechanisms Of Action ◽  
Experimental Models ◽  
Inflammatory Activity ◽  
Chemical Structures ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

This review is aimed at presenting relevant information on the therapeutic potential of essential oil sesquiterpenes with anti-inflammatory activity. The data reviewed provide a basis for seeking new anti-inflammatory drugs from natural products that do not exhibit the undesirable side effects often displayed by anti-inflammatory drugs. In this review the experimental models, possible mechanisms of action, and chemical structures of 12 sesquiterpenes are presented.

scholarly journals Thiophene-Based Compounds with Potential Anti-Inflammatory Activity

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.

scholarly journals Evaluation of Anticonvulsant Activity of Dual COX-2/5-LOX Inhibitor Darbufelon and Its Novel Analogues

2021 ◽  
Vol 89 (2) ◽  
pp. 22
Author(s):  
Mariia Mishchenko ◽  
Sergiy Shtrygol’ ◽  
Andrii Lozynskyi ◽  
Semen Khomyak ◽  
Volodymyr Novikov ◽  
...  
Keyword(s):  
Drug Design ◽  
Anticonvulsant Activity ◽  
Inflammatory Activity ◽  
Significant Protection ◽  
Protection Level ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Target Agent

Neuroinflammation is an integral part of epilepsy pathogenesis and other convulsive conditions, and non-steroidal anti-inflammatory drugs (NSAIDs) present a potent tool for the contemporary search and design of novel anticonvulsants. In the present paper, evaluation of the anticonvulsant activity of the potential NSAID dual COX-2/5-LOX inhibitor darbufelone methanesulfonate using an scPTZ model in mice in dose 100 mg/kg is reported. Darbufelone possesses anticonvulsant properties in the scPTZ model and presents interest for in-depth studies as a possible anticonvulsant multi-target agent with anti-inflammatory activity. The series of 4-thiazolidinone derivatives have been synthesized following the analogue-based drug design and hybrid-pharmacophore approach using a darbufelone matrix. The synthesized derivatives showed a significant protection level for animals in the scPTZ model and are promising compounds for the design of potential anticonvulsants with satisfactory drug-like parameters.

Adverse reactions with the use of non-steroidal anti-inflammatory drugs

2020 ◽  
pp. 35-50
Author(s):  
M. L. Maksimov ◽  
N. M. Kiseleva ◽  
D. G. Semenikhin ◽  
B. K. Romanov
Keyword(s):  
Risk Factors ◽  
Adverse Reactions ◽  
Effective Prevention ◽  
Chemical Structures ◽  
Wide Range ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Prevention Method ◽  
Effective Medication ◽  
Upper Gastrointestinal

Non-steroidal anti-inflammatory drugs (NSAIDs) are included in a pharmacological group of drugs with different chemical structures providing anti-inflammatory, analgesic and antipyretic actions, as well as antiplatelet action to a certain degree. Unfortunately, NSAIDs can cause a wide range of adverse reactions (AR) posing a serious risk to the health and life of patients. Therefore, the rational use of NSAIDs should include methods for effective prevention of drug complications. Many NSAIDs have a pronounced therapeutic effect, simultaneously causing many undesirable effects, so the drug shall be chosen considering the development of predicted side effects and modern algorithms. According to clinical recommendations, risk factors and administration of safer NSAIDs shall be considered as the main prevention method. Besides, it is possible to protect the patient from the upper gastrointestinal tract complications using proton pump inhibitors. It should be noted that there are no effective medication methods for kidney and liver protection to reduce the risk of NSAID-associated complications.

AN UPDATE ON THE SYNTHESIS OF BENZOXAZOLES

2017 ◽  
Vol 10 (10) ◽  
pp. 48 ◽  
Author(s):  
Jyothi M ◽  
Ramchander Merugu
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Biological Activity ◽  
Biological Activities ◽  
Starting Material ◽  
Bioactive Molecules ◽  
Living Systems ◽  
Inflammatory Activity ◽  
Anti Inflammatory

Benzoxazoles being structurally similar to bases adenine and guanine interact with biomolecules present in living systems. These compounds possess antimicrobial, central nervous system activities, antihyperglycemic potentiating activity, analgesic, and anti-inflammatory activity. It can also be used as starting material for other bioactive molecules. Modifications in structure and the biological profiles of new generations of benzoxazoles were found to be more potent with enhanced biological activity. Considering all these, we have prepared this review and discussed the synthesis and biological activities of benzoxazoles.

scholarly journals SYNTHESIS NEW POTENTIAL ANTI-INFLAMMATORY AGENT SODIUM SALT OF PENTAGAMAVUNON-0

2010 ◽  
Vol 4 (3) ◽  
pp. 180-185
Author(s):  
Enade Perdana Istyastono ◽  
Rr. Sri Untari Siwi S.M.P ◽  
Andreas Asdi Utama ◽  
Supardjan A.M
Keyword(s):  
Inflammatory Activity ◽  
Physiological Changes ◽  
Solubility In Water ◽  
Curcumin Analogues ◽  
Inflammatory Agent ◽  
Curcumin Derivatives ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Living Tissues ◽  
Anti Inflammation

Inflammation is the response of living tissues to injury. The process affects physiological changes such as erythema, edema, asthma and fever. Non-steroid Anti-inflammatory Drugs (NSAIDs) have been developed since they could inhibit inflammation process because of its ability to inhibit biosynthesis of prostaglandin, one of inflammation mediators, through inhibition of cyclooxigenase (COX) enzymes. Molecules, which have been reported having anti-inflammatory activity, for example, are curcumin, some curcumin derivatives and curcumin analogues. One of curcumin analogues that has been  developed is pentagamavunon-0 (PGV-0) whose IUPAC name is 2,5-bis(4'-hidroxy-3'-methoxy-benzylidene)cyclo-pentanone. But PGV-0, which is like curcumin, practically insoluble in water, so it causes problems in the development. The aim of this research is to synthesize a derivative of PGV-0, a natrium salt of PGV-0 (natrium pentagamavunonate-0/Na-pentagamavunonate-0), which is hoped to have a better anti-inflammatory activity and solubility in water than PGV-0. PGV-0 was synthesized by reacting vanillin and cyclopentanone catalized by acid. Na-pentagamavunonate-0 was synthesized with PGV-0 as a starting material using an appropriate method. This research was able to synthesize new compound that was estimated as a natrium salt of PGV-0 (natrium pentagamavunonate-0/Na-pentagamavunonate-0).   Keywords: Curcumin, PGV-0, Na-pentagamavunonate-0, anti-inflammation

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