Substituted 3-R-2,8-Dioxo-7,8-dihydro-2H-pyrrolo[1,2-a][1,2,4]triazino-[2,3-c]quinazoline-5a(6H)carboxylic Acids and Their Salts – a Promising Class of Anti-inflammatory Agents

2020 ◽  
Vol 19 ◽  
Author(s):  
Viktor Stavytskyi ◽  
Oleksii Antypenko ◽  
Inna Nosulenko ◽  
Galyna Berest ◽  
Oleksii Voskoboinik ◽  
...  
Keyword(s):  
Carboxylic Acids ◽  
Molecular Mechanisms ◽  
Molecular Targets ◽  
Docking Study ◽  
Inflammatory Activity ◽  
Reference Drug ◽  
Antiinflammatory Agents ◽  
In Vivo Experiments ◽  
Anti Inflammatory

Background: Computer aided drug design is among the most effective methods of medicinal chemistry. Abovementioned approaches were used for purposeful search of antiinflammatory agents among quinazoline condensed derivatives. Objective: Purposeful synthesis of novel 3-R-2,8-dioxo-7,8-dihydro-2H-pyrrolo[1,2- a][1,2,4]triazino[2,3-c]quinazoline-5a(6H)carboxylic acids and their salts as promising antiinflammatory agents, evaluation of their structure by physicochemical methods and establishing of their anti-inflammatory activity. Methods: The structures of target compounds were proposed due to their structure similarity to existing drugs and experimental agents with anti-inflammatory activity. The features of the synthesized compounds structures were evaluated by IR-, NMR spectroscopy and chromatographymass spectrometry and were discussed in detail. Probable molecular mechanisms of activity were predicted by molecular docking. The anti-inflammatory activity was determined by their ability to reduce the formalin- and carrageenan-induced paw edema in rats. Results: It was found, that condensation of 3-(2-aminophenyl)-6-R-1,2,4-triazin-5(2H)ones with 2- oxoglutaric acid yielded 3-R-2,8-dioxo-7,8-dihydro-2H-pyrrolo[1,2-a][1,2,4]triazino[2,3- c]quinazoline-5a(6H)carboxylic acids which may be considered as a promising anti-inflammatory agents. In silico study showed, that obtained compounds revealed affinity to the molecular targets and corresponded to the «drug-like» criteria. Additionally docking study allowed to estimate the nature of interactions between synthesized compounds and molecular targets. The in vivo experiments showed that obtained compounds demonstrated the significant anti-inflammatory activity comparable or higher than activity of the reference drug «Diclofenac». Conclusion: The developed and implemented search strategy of the anti-inflammatory agents was justified. 3-R-2,8-dioxo-7,8-dihydro-2H-pyrrolo[1,2-a][1,2,4]triazino[2,3-c]quinazoline5a(6H)carboxylic acids possessed the mentioned activity and additional introduction of fluorine atoms in position 11 or 12 of the heterocyclic system led to amplification of anti-inflammatory activity.

scholarly journals Synthesis, Anti-Inflammatory Activity, and In Silico Study of Novel Diclofenac and Isatin Conjugates

2018 ◽  
Vol 2018 ◽  
pp. 1-11
Author(s):  
Musab Mohamed Ibrahim ◽  
Tilal Elsaman ◽  
Mosab Yahya Al-Nour
Keyword(s):  
Virtual Screening ◽  
Condensation Reaction ◽  
Docking Study ◽  
Positive Control ◽  
Inflammatory Activity ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Chemical Structures ◽  
Anti Inflammatory

The design, synthesis, and development of novel non-steroidal anti-inflammatory drugs (NSAIDs) with better activity and lower side effects are respectable area of research. Novel Diclofenac Schiff’s bases (M1, M2, M4, M7, and M8) were designed and synthesized, and their respective chemical structures were deduced using various spectral tools (IR, 1H NMR, 13C NMR, and MS). The compounds were synthesized via Schiff’s condensation reaction and their anti-inflammatory activity was investigated applying the Carrageenan-induced paw edema model against Diclofenac as positive control. Percentage inhibition of edema indicated that all compounds were exhibiting a comparable anti-inflammatory activity as Diclofenac. Moreover, the anti-inflammatory activity was supported via virtual screening using molecular docking study. Interestingly compound M2 showed the highest in vivo activity (61.32% inhibition) when compared to standard Diclofenac (51.36% inhibition) as well as the best binding energy score (-10.765) and the virtual screening docking score (-12.142).

In vivo anti-inflammatory activity and docking study of newly synthesized benzimidazole derivatives bearing oxadiazole and morpholine rings

2017 ◽  
Vol 70 ◽  
pp. 107-117 ◽  
Author(s):  
Ankita Rathore ◽  
Raja Sudhakar ◽  
Mohamed Jawed Ahsan ◽  
Abuzer Ali ◽  
Naidu Subbarao ◽  
...  
Keyword(s):  
Docking Study ◽  
Inflammatory Activity ◽  
Benzimidazole Derivatives ◽  
Anti Inflammatory

scholarly journals Biological Evaluation and Docking Analysis of Daturaolone as Potential Cyclooxygenase Inhibitor

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Abdur Rauf ◽  
Francesco Maione ◽  
Ghias Uddin ◽  
Muslim Raza ◽  
Bina S. Siddiqui ◽  
...  
Keyword(s):  
In Silico ◽  
Biological Evaluation ◽  
Inflammatory Activity ◽  
Active Constituent ◽  
Ligand Complex ◽  
Reference Drug ◽  
Paw Oedema ◽  
Anti Inflammatory ◽  
Dose Dependent

This study deals with the isolation of the active constituent(s) from a methanolic extract ofPistacia integerrimaJ. L. Stewart barks and it was also oriented to evaluate thein vivoandin silicoanti-inflammatory activity. By NMR and crystallography techniques, we have isolated a triterpenoid identified as daturaolone (compound1). This compound showedin vivoa significant and dose dependent (1–30 mg/kg) anti-inflammatory activity on carrageenan-induced mouse paw oedema (ED50= 10.1 mg/kg) and on acetic acid-induced writhing responses in mice (ED50= 13.8 mg/kg). In thein vivoexperiments, the effect of tested compound was also evaluated in presence of the reference drug diclofenac (1–30 mg/kg). Moreover,in silicoanalysis of receptor ligand complex shows that compound1interacts with cyclooxygenases (COXs) binding sites displaying an interesting interaction with COX-1. These findings suggest that compound1isolated fromP.integerrimapossessesin vivoanti-inflammatory and antinociceptive potentials, which are supportedin silicoby an interaction with COXs receptors.

scholarly journals Aspirin-Based Organoiron Dendrimers as Promising Anti-Inflammatory, Anticancer, and Antimicrobial Drugs

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1568
Author(s):  
Alaa S. Abd-El-Aziz ◽  
Maysun R. Benaaisha ◽  
Amani A. Abdelghani ◽  
Rabin Bissessur ◽  
Laila H. Abdel-Rahman ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Inflammatory Activity ◽  
Breast Cancer Cell Lines ◽  
Cell Viability Assay ◽  
Reference Drug ◽  
Anti Inflammatory

Designing nanocarriers with actions directed at a specific organ or tissue is a very promising strategy since it can significantly reduce the toxicity of a bioactive drug. In this study, an organometallic dendrimer was used to synthesize a biocompatible drug delivery system by attaching aspirin to the periphery of the dendrimer. Our goal is to enhance the bioavailability and anticancer activity of aspirin and reduce its toxicity through successive generations of organoiron dendrimers. The biological activity of aspirin-based dendrimer complexes was evaluated. The result of antimicrobial activity of the synthesized dendrimers also demonstrated an increase in their antimicrobial activity with increased generation of the dendrimers for most types of microorganisms. This study reveals for the first time that organoiron dendrimers linked with aspirin exhibit an excellent Gram-negative activity comparable to the reference drug Gentamicin. All synthesized dendrimers were tested for their anticancer activity against breast cancer cell lines (MCF-7), hepatocellular cell lines (Hep-G2), and a non-cancer cell line, Human Embryonic Kidney (HEK293), using the MTT cell viability assay and compared against a standard anticancer drug, Doxorubicin. Compounds G3-D9-Asp and G4-D12-Asp exhibited noticeable activity against both cell lines, both of which were more effective than aspirin itself. In addition, the in vivo anti-inflammatory activity and histopathology of swollen paws showed that the designed aspirin-based dendrimers displayed significant anti-inflammatory activity; however, G2-D6-Asp showed the best anti-inflammatory activity, which was more potent than the reference drug aspirin during the same period. Moreover, the coupling of aspirin to the periphery of organoiron dendrimers showed a significant reduction in the toxicity of aspirin on the stomach.

scholarly journals Directed Search of Anti-inflammatory Agents Among (3HQuinazoline- 4-ylidene)hydrazides of N-protected Amino acids and their Heterocyclization Products

2020 ◽  
Vol 19 (1) ◽  
pp. 61-73
Author(s):  
Yulya Martynenko ◽  
Oleksii Antypenko ◽  
Inna Nosulenko ◽  
Galina Berest ◽  
Sergii Kovalenko
Keyword(s):  
Amino Acids ◽  
Molecular Mechanisms ◽  
Diclofenac Sodium ◽  
Inflammatory Activity ◽  
Directed Search ◽  
Reference Drug ◽  
Aryl Amines ◽  
Anti Inflammatory ◽  
Sar Analysis ◽  
Cox 1

Background: (Quinazoline-4-ylidene)hydrazides are valued intermediates in modern organic chemistry, as they are commonly used for the synthesis of substituted [1,2,4]triazolo[1,5-c]quinazolines. Objective: Unknown N-acyl-2-([1,2,4]triazolo[1,5-c]quinazoline-2-yl)-alkyl-(alkaryl-, aryl-) amines were synthesized and evaluated for anti-inflammatory potential. Methods: The peculiarities of the synthesized compounds structures were studied by IR-, NMR spectroscopy and chromatography-mass spectrometry and were discussed in detail. Probable molecular mechanisms of activity (inhibition of COX-1 and COX-2) were predicted due to molecular docking. Anti-inflammatory activity of synthesized compounds was determined by their ability to reduce the formalin-induced paw edema in rats. Diclofenac sodium was used as reference drug. Results: In this study, the synthesis of N-acetyl-(benzoyl)-2-([1,2,4]triazolo[1,5-c]quinazolinе- 2-yl)alkyl-(aralkyl-, aryl-)amines, using (3H-quinazoline-4-ylidene)hydrazides of Nprotected amino acids or 4-hydrazinoquinazoline and N-prorotected amino acids as starting compounds was developed. It was established that the reaction of (3H-quinazoline-4- ylidene)hydrazides of Boc-amino acids occurred with the formation of N-acetyl-substituted triazoloquinazolines. High anti-inflammatory activity was detected for unknown (3Hquinazoline- 4-ylidene)hydrazides Boc-amino acids (1.13-1.15) and N-acetyl-(benzoyl)-2- ([1,2,4]triazolo[1,5-c]quinazoline-2-yl-)aralkyl-(aryl-)amines (3.2, 3.3, 3.11, 3.12), using the experimental formalin test. Conclusion: The conducted SAR-analysis allowed to detect critical fragments. Namely, the Boc-aminoaralkyl-(aryl-)acid residue in (3H-quinazoline-4-ylidene)hydrazides (1.13- 1.15), benzyl and phenyl linker groups in N-acetyl-(benzoyl)-2-([1,2,4]triazolo[1,5- c]quinazoline-2-yl-)aralkyl-(aryl-) amines (3.2, 3.3, 3.11, 3.12) are believed to be substantial for anti-inflammatory activity.

scholarly journals The Dietary Flavonoid Kaempferol Mediates Anti-Inflammatory Responses via the Src, Syk, IRAK1, and IRAK4 Molecular Targets

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Shi Hyoung Kim ◽  
Jae Gwang Park ◽  
Jongsung Lee ◽  
Woo Seok Yang ◽  
Gye Won Park ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Molecular Targets ◽  
Peritoneal Macrophages ◽  
Cellular Adhesion ◽  
Inflammatory Activity ◽  
Prostaglandin E ◽  
Genes Encoding ◽  
Anti Inflammatory

Even though a lot of reports have suggested the anti-inflammatory activity of kaempferol (KF) in macrophages, little is known about its exact anti-inflammatory mode of action and its immunopharmacological target molecules. In this study, we explored anti-inflammatory activity of KF in LPS-treated macrophages. In particular, molecular targets for KF action were identified by using biochemical and molecular biological analyses. KF suppressed the release of nitric oxide (NO) and prostaglandin E2(PGE2), downregulated the cellular adhesion of U937 cells to fibronectin (FN), neutralized the generation of radicals, and diminished mRNA expression levels of inflammatory genes encoding inducible NO synthase (iNOS), TNF-α, and cyclooxygenase- (COX-) 2 in lipopolysaccharide- (LPS-) and sodium nitroprusside- (SNP-) treated RAW264.7 cells and peritoneal macrophages. KF reduced NF-κB (p65 and p50) and AP-1 (c-Jun and c-Fos) levels in the nucleus and their transcriptional activity. Interestingly, it was found that Src, Syk, IRAK1, and IRAK4 responsible for NF-κB and AP-1 activation were identified as the direct molecular targets of KF by kinase enzyme assays and by measuring their phosphorylation patterns. KF was revealed to havein vitroandin vivoanti-inflammatory activity by the direct suppression of Src, Syk, IRAK1, and IRAK4, involved in the activation of NF-κB and AP-1.

scholarly journals The Anti-Inflammatory Activity of HMGB1 A Box Is Enhanced When Fused with C-Terminal Acidic Tail

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Wei Gong ◽  
Yingru Zheng ◽  
Fan Chao ◽  
Yuan Li ◽  
Zhizhen Xu ◽  
...  
Keyword(s):  
Fusion Proteins ◽  
Inflammatory Diseases ◽  
Inflammatory Activity ◽  
In Vivo Experiments ◽  
Specific Antagonist ◽  
Proinflammatory Activity ◽  
Anti Inflammatory ◽  
Inflammatory Effect

HMGB1, composed of the A box, B box, and C tail domains, is a critical proinflammatory cytokine involved in diverse inflammatory diseases. The B box mediates proinflammatory activity, while the A box alone acts as a specific antagonist of HMGB1. The C tail contributes to the spatial structure of A box and regulates HMGB1 DNA binding specificity. It is unknown whether the C tail can enhance the anti-inflammatory effect of A box. In this study, we generated fusion proteins consisting of the A box and C tail, in which the B box was deleted and the A box and C tail were linked either directly or by the flexible linker sequence(Gly4Ser)3. In vitro and in vivo experiments showed that the two fusion proteins had a higher anti-inflammatory activity compared to the A box alone. This suggests that the fused C tail enhances the anti-inflammatory effect of the A box.

scholarly journals The research of anti-inflammatory activity of 5-(5-bromofuran-2-yl)-4-ethyl-1,2,4-triazole-3-thion S-derivatives

2018 ◽  
pp. 78-82
Author(s):  
Ye. S. Pruglo
Keyword(s):  
Bromine Atom ◽  
Pharmacological Action ◽  
Inflammatory Activity ◽  
The Novel ◽  
Dimethylamino Group ◽  
Reference Drug ◽  
White Rats ◽  
Anti Inflammatory ◽  
Inflammatory Action

The studing of  anti-inflammatory activity of the novel compounds may give rise to the using of safer and more active drugs in the treatment of diseases which are shown NSAIDs. To further study the pharmacological properties of the synthesized c compounds were studied for acute toxicity and anti-inflammatory activity of 5-thio derivates of 3-(5-вromofuran-2-yl)-4-ethyl-(4H)-1,2,4-triazole at white rats by formalin method of acute edema. After investigation of anti-inflammatory activity in vivo of first synthesized 1,2,4-triazole derivatives it was found that potassium salt of 2-(4-ethyl-5-(5-bromfuran-2-yl)-1,2,4-triazoles 3-iltio) acetic acid (Compound 24) had the most significant anti-inflammatory activity. This compound suppressed the formation of edema quotes of rats at 59.87% and was more active than the reference drug diclofenac at 15.13%. There were established the patterns regarding chemical structure and pharmacological action of these substances. So replacing of bromine atom at the dimethylamino group in the para-position of the phenyl radical in the molecule of N'-(4-brombenzyliden)-2-((5-(5-bromfuran-2-yl)-4-ethyl-4H-1,2,4-triazole-3-yl)tio)acetic hydrazid (Compound 36) was accompanied by appearence of the anti-inflammatory action. It was revealed that in the number from the ammonium salt (Compound 30) to monoethanolamonium salt (Compound 23) and to the morpholinum salt (Compound 22) it was observed an increase of inflammation and probably growing number of pro-inflammatory mediators released.

Evidence for the anti-inflammatory activity of Bupleurum marginatum (Apiaceae) extracts using in vitro and in vivo experiments supported by virtual screening

2018 ◽  
Vol 70 (7) ◽  
pp. 952-963 ◽  
Author(s):  
Mohamed L. Ashour ◽  
Fadia S. Youssef ◽  
Haidy A. Gad ◽  
Mahmoud Z. El-Readi ◽  
Amel Bouzabata ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Inflammatory Activity ◽  
In Vivo Experiments ◽  
Anti Inflammatory

Detection of cysteine-rich peptides in Tragia benthamii Baker (Euphorbiaceae) and in vivo antiinflammatory effect in a chick model

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Alfred F. Attah ◽  
Abobarin I. Omobola ◽  
Jones O. Moody ◽  
Mubo A. Sonibare ◽  
Olubori M. Adebukola ◽  
...  
Keyword(s):  
Body Weight ◽  
Brine Shrimp ◽  
Scientific Evidence ◽  
Biologically Active ◽  
Inflammatory Activity ◽  
Reference Drug ◽  
Aqueous Fraction ◽  
Brine Shrimp Lethality Assay ◽  
Anti Inflammatory

Abstract Tragia benthamii (TBM) commonly called the climbing nettle is a tropical plant claimed to have numerous anti inflammatory effects in sub Saharan African ethnomedicine which lacks scientific evidence. Aqueous extracts of TBM were further prepurified on a RP-C18 parked solid phase system to obtain 20% aqueous fraction. This fraction was enzymatically and chemically analyzed (by MALDI TOF MS and MS/MS) to contain interesting low molecular weight cysteine-rich stable peptides within the range of 2.5–3.2 KDa. The 20% aqueous fraction was further tested in vivo using carrageenan-induced foot edema (acute inflammation) in seven-day old chicks with diclofenac as reference drug. The cytotoxicity of this active fraction was investigated using the brine shrimp lethality assay. The brine shrimp cytotoxicity assay produced LC50 above 1000 μg/mL. Pretreatment with the TBM extract (30–300 mg/kg, i.p) dose dependently (P<0.01) reduced foot edema with maximal inhibition of 0.253 ± 0.180 (84.3%) at 300 mg/kg body weight, which was comparable to that of diclofenac with inhibition (P<0.05) of 0.410 ± 0.271 (74.5%) at 10 mg/kg body weight. The study has therefore shown for the first time, the detection of cysteine-rich biologically active peptides in T. benthamii and the stable peptide extracts from this ethnomedicinal plant, which is not toxic to Artemia salina, exhibits anti inflammatory activity in a chick in vivo model. This may provide scientific evidence for its use in the treatment of inflammation and pain in traditional medicine. Further in-depth vivo and in vitro studies will be required to investigate its anti inflammatory activity including effect on HUVEC-TERT, the possible inhibition of ICAM-1 surface expression and the mechanism of the anti inflammatory effect.

Sign in / Sign up

Export Citation Format

Share Document