Synthesis and Biological Evaluation of 1,3,5‐Trisubstituted 2‐Pyrazolines as Novel Cyclooxygenase‐2 Inhibitors with Antiproliferative Activity

Vahedpour, Teymour; Kaur, Jatinder; Hemmati, Salar; Hamzeh‐Mivehroud, Maryam; Alizadeh, Ali Akbar; Wuest, Frank; Dastmalchi, Siavoush

doi:10.1002/cbdv.202000832

Cited by 5 publications

(5 citation statements)

References 37 publications

(43 reference statements)

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“…The anti-inflammatory, analgesic, antipyretic, and anticoagulant effects of NSAIDs result from blocking the COX-2 enzyme. On the other hand, the inhibition of physiological prostaglandin production by COX-1 blockade is the cause of most of the side effects of NSAIDs [ 75 , 76 ]. In addition, selective COX-2 inhibitors present chemopreventive activity in colorectal cancer [ 77 ].…”

Section: Discussionmentioning

confidence: 99%

Design, Synthesis, Biological Evaluation, and Molecular Docking Study of 4,6-Dimethyl-5-aryl/alkyl-2-[2-hydroxy-3-(4-substituted-1-piperazinyl)propyl]pyrrolo[3,4-c]pyrrole-1,3(2H,5H)-diones as Anti-Inflammatory Agents with Dual Inhibition of COX and LOX

et al. 2023

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In the present study, we characterize the biological activity of a newly designed and synthesized series of 15 compounds 2-[2-hydroxy-3-(4-substituted-1-piperazinyl)propyl] derivatives of pyrrolo[3,4-c]pyrrole 3a–3o. The compounds were obtained with good yields of pyrrolo[3,4-c]pyrrole scaffold 2a–2c with secondary amines in C2H5OH. The chemical structures of the compounds were characterized by 1H-NMR, 13C-NMR, FT-IR, and MS. All the new compounds were investigated for their potencies to inhibit the activity of three enzymes, i.e., COX-1, COX-2, and LOX, by a colorimetric inhibitor screening assay. In order to analyze the structural basis of interactions between the ligands and cyclooxygenase/lipooxygenase, experimental data were supported by the results of molecular docking simulations. The data indicate that all of the tested compounds influence the activity of COX-1, COX-2, and LOX.

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Section: Discussionmentioning

confidence: 99%

Design, Synthesis, Biological Evaluation, and Molecular Docking Study of 4,6-Dimethyl-5-aryl/alkyl-2-[2-hydroxy-3-(4-substituted-1-piperazinyl)propyl]pyrrolo[3,4-c]pyrrole-1,3(2H,5H)-diones as Anti-Inflammatory Agents with Dual Inhibition of COX and LOX

et al. 2023

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“…[49] In another study by our group, various 1,3,5-trisubstituted 2-pyrazolines were prepared without catalyst in the cyclization step. [50] The prepared chalconic compound…”

Section: Reactions Without Using Catalystmentioning

confidence: 99%

“…In another study by our group, various 1,3,5‐trisubstituted 2‐pyrazolines were prepared without catalyst in the cyclization step [50] . The prepared chalconic compound 35 a was reacted with hydrazine hydrate 35 b in ethanol under reflux conditions to obtain N1‐unsubstituted 2‐pyrazoline 35 c , which was treated with various acyl chlorides 35 d or isocyanates 35 e and 35 f to yield 2‐pyrazolines 35 g , 35 h , 35 i (Scheme 35).…”

Section: Synthetic Strategiesmentioning

confidence: 99%

Synthesis of 2‐Pyrazolines from Hydrazines: Mechanisms Explained

et al. 2021

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2-Pyrazoline core is a very interesting five-membered heterocycle, which has been explored in recent years due to its vast applications as the core structure of bioactive and industrial agents. Based on literature studies, versatile synthetic approaches have been employed for the preparation of 2pyrazolines, among them the reaction between hydrazines and α,β-unsaturated enones as the most used method. In this review article, different methods for the synthesis of 2-pyrazolines using hydrazine derivatives were classified and presented.Initially, numerous catalytic methods for the preparation of 2pyrazolines from hydrazines and α,β-unsaturated enones are reviewed and various aspects of these methods discussed including catalyst efficiency, catalyst recovery, green chemistry, cost-effectiveness, scope of the method, enantioselectivity, and yield. In addition, reactions between hydrazines and other reagents in multicomponent and two-component reactions, developed recently, are discussed. Finally, some of the important applications of 2-pyrazolines are summarized.

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“…Several nonsteroidal anti-inflammatory drugs (NSAIDs) exert their effect by inhibiting cyclooxygenases (COXs) which catalyzes the of arachidonic acid (AA) metabolism in prostaglandins (PGs) and thromboxanes (TXs) [6,7]. COX was shown to exhibit three isoforms, those being COX-1, COX-2 and COX-3 [8]. The constitutive enzyme COX-1 is involved in the production of physiological PGs and TXs which control, respectively, the protection of the gastric mucosa, kidney function and platelet aggregation, acting as a "housekeeper" enzyme [7,9,10].…”

Section: Introductionmentioning

confidence: 99%

Phytochemical Characterization, Antioxidant and Anti-Inflammatory Effects of Cleome arabica L. Fruits Extract against Formalin Induced Chronic Inflammation in Female Wistar Rat: Biochemical, Histological, and In Silico Studies

et al. 2022

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In recent decades, the use of herbs and plants has been of great interest, as they have been the sources of natural products, commonly named as bioactive compounds. In specific, the natural compounds from the Capparaceae family which has been proved to have antioxidant, anti-inflammatory, antimicrobial and anti-carcinogenic activities, by several studies. Cleome arabica L. (CA) specie is the most used medicinal plants in Tunisia and elsewhere in North African countries for treatment of various diseases including diabetes, rheumatism, inflammation, cancer, and digestive disorders. The current work was undertaken to estimate the total phenolic, flavonoid and condensed tannin contents, to identify and quantify the polyphenolic compounds, and to evaluate the antioxidant and the anti-inflammatory proprieties of CA fruits extract against formalin induced chronic inflammation in Female Wistar rats. In fact, the antioxidant activity was tested by Diphenyl-1-Picrylhydrazyl free radical scavenging (DPPH), Ferric reducing antioxidant power (FRAP) and Nitric Oxide radical (NO·). Anti-inflammatory effect of fruits extract was examined using formalin (2%) induced paw edema in rats. Molecular docking tools were used to investigate the interaction of some compounds from CA fruits extract with the cyclooxygenase-2 (COX-2) target protein. Our results showed that, the total phenolic, flavonoid and tannins contents, which were assessed by the Folin-Ciocalteu, Quercetin, and Catechin methods, respectively, were 230.22 mg gallic acid equivalent/g dry weight (mg GAE/g DW), 55.08 mg quercetin equivalent/g dry weight (QE/g DW) and 15.17 mg catechin equivalents/g dry weight (CatE/g DW), respectively. HPLC analysis revealed the presence of five polyphenolic compounds whose catechin was found to be the most abundant compounds. The antioxidant activity of extract was quantified by DPPH, FRAP and NO· tests and IC50 reached the values of 3.346 mg/mL, 2.306 and 0.023 mg/mL, respectively. Cleome fruits ameliorated the histological integrity of the skin and alleviated the disruptions in hematological parameters (WBC, LYM, RBC, and HGB), inflammatory cytokines (IL-1β, IL-6, TNF-α), C-reactive protein, and some oxidative stress markers (TBARS (−49%) and AOPP (−42%) levels, SOD (+33%) and GPx (+75%) activities, and GSH (+49%) content) induced by formalin injection. Moreover, the in-silico investigation had shown that CA fruits extract compounds have a stronger interaction with COX-2 active site, more than the reference drug “indomethacin” (two H-bonds). Our research gives pharmacological backing to the healthcare utilization of Cleome plant in the treatment of inflammatory diseases and oxidative harm.

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Synthesis and Biological Evaluation of 1,3,5‐Trisubstituted 2‐Pyrazolines as Novel Cyclooxygenase‐2 Inhibitors with Antiproliferative Activity

Cited by 5 publications

References 37 publications

Design, Synthesis, Biological Evaluation, and Molecular Docking Study of 4,6-Dimethyl-5-aryl/alkyl-2-[2-hydroxy-3-(4-substituted-1-piperazinyl)propyl]pyrrolo[3,4-c]pyrrole-1,3(2H,5H)-diones as Anti-Inflammatory Agents with Dual Inhibition of COX and LOX

Design, Synthesis, Biological Evaluation, and Molecular Docking Study of 4,6-Dimethyl-5-aryl/alkyl-2-[2-hydroxy-3-(4-substituted-1-piperazinyl)propyl]pyrrolo[3,4-c]pyrrole-1,3(2H,5H)-diones as Anti-Inflammatory Agents with Dual Inhibition of COX and LOX

Synthesis of 2‐Pyrazolines from Hydrazines: Mechanisms Explained

Phytochemical Characterization, Antioxidant and Anti-Inflammatory Effects of Cleome arabica L. Fruits Extract against Formalin Induced Chronic Inflammation in Female Wistar Rat: Biochemical, Histological, and In Silico Studies

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