Synthesis, evaluation and docking studies of some 4-thiazolone derivatives as effective lipoxygenase inhibitors

Synthesis, evaluation and docking studies of some 4-thiazolone derivatives as effective... Some promising 4-thiazolone derivatives as lipoxygenase inhibitors were designed, synthesized, characterized and evaluated for anti-inflammatory activity and respective ulcerogenic liabilities. Compounds (1b, 1e, 3b, and 3e) exhibited considerable in vivo anti-inflammatory activity (57.61, 79.35, 75.00, and 79.35%) against carrageenan-induced rat paw edema model, whereas compounds (1e, 3b, and 3e) were found active against the arachidonic acid-induced paw edema model (55.38, 55.38, and 58.46%). The most potent compound (3e) exhibited lesser ulcerogenic liability compared to the standard diclofenac and zileuton. Further, the promising compounds (1e and 3e) were evaluated for in vitro lipoxygenase (LOX; IC50 = 12.98 µM and IC50 = 12.67 µM) and cyclooxygenase (COX) inhibition assay (COX-1; IC50 > 50 µM and, COX-2; IC50 > 50 µM). The enzyme kinetics of compound 3e was evaluated against LOX enzyme and supported by in silico molecular docking and molecular dynamics simulations studies. Overall, the results substantiated that 5-benzylidene-2-phenyl-4-thiazolones are promising pharmacophore for anti-inflammatory activity. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Chemical Papers Springer Journals

Synthesis, evaluation and docking studies of some 4-thiazolone derivatives as effective lipoxygenase inhibitors

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Publisher
Springer Journals
Copyright
Copyright © 2018 by Institute of Chemistry, Slovak Academy of Sciences
Subject
Chemistry; Chemistry/Food Science, general; Industrial Chemistry/Chemical Engineering; Biochemistry, general; Medicinal Chemistry; Materials Science, general; Biotechnology
ISSN
0366-6352
eISSN
1336-9075
D.O.I.
10.1007/s11696-018-0520-9
Publisher site
See Article on Publisher Site

Abstract

Some promising 4-thiazolone derivatives as lipoxygenase inhibitors were designed, synthesized, characterized and evaluated for anti-inflammatory activity and respective ulcerogenic liabilities. Compounds (1b, 1e, 3b, and 3e) exhibited considerable in vivo anti-inflammatory activity (57.61, 79.35, 75.00, and 79.35%) against carrageenan-induced rat paw edema model, whereas compounds (1e, 3b, and 3e) were found active against the arachidonic acid-induced paw edema model (55.38, 55.38, and 58.46%). The most potent compound (3e) exhibited lesser ulcerogenic liability compared to the standard diclofenac and zileuton. Further, the promising compounds (1e and 3e) were evaluated for in vitro lipoxygenase (LOX; IC50 = 12.98 µM and IC50 = 12.67 µM) and cyclooxygenase (COX) inhibition assay (COX-1; IC50 > 50 µM and, COX-2; IC50 > 50 µM). The enzyme kinetics of compound 3e was evaluated against LOX enzyme and supported by in silico molecular docking and molecular dynamics simulations studies. Overall, the results substantiated that 5-benzylidene-2-phenyl-4-thiazolones are promising pharmacophore for anti-inflammatory activity.

Journal

Chemical Papers – Springer Journals

Published: Jun 1, 2018

References

  • Synthesis and three-dimensional qualitative structure selectivity relationship of 3, 5-disubstituted-2, 4-thiazolidinedione derivatives as COX2 inhibitors
    Ali, AM; Saber, GE; Mahfouz, NM; El-Gendy, MA; Radwan, AA; Hamid, MA
  • Non-steroid anti-inflammatory drugs, prostaglandins, and cancer
    Allaj, V; Guo, C; Nie, D
  • Structure and ligand based drug design strategies in the development of novel 5-LOX inhibitors
    Aparoy, P; Kumar Reddy, K; Reddanna, P
  • Synthesis, characterization, evaluation and molecular dynamics studies of 5, 6–diphenyl–1, 2, 4–triazin–3 (2H)–one derivatives bearing 5–substituted 1, 3, 4–oxadiazole as potential anti–inflammatory and analgesic agents
    Banerjee, AG; Das, N; Shengule, SA; Srivastava, RS; Shrivastava, SK
  • Design, synthesis, evaluation and molecular modelling studies of some novel 5, 6-diphenyl-1, 2, 4-triazin-3 (2H)-ones bearing five-member heterocyclic moieties as potential COX-2 inhibitors: A hybrid pharmacophore approach
    Banerjee, AG; Das, N; Shengule, SA; Sharma, PA; Srivastava, RS; Shrivastava, SK
  • A química medicinal de N-acilidrazonas: Novos compostos-protótipos de fármacos analgésicos, antiinflamatórios e anti-trombóticos
    Barreiro, EJ; Fraga, CA; Miranda, AL; Rodrigues, CR
  • Synthesis and biological evaluation of a class of 5-benzylidene-2-phenyl-thiazolinones as potent 5-lipoxygenase inhibitors
    Barzen, S; Rödl, CB; Lill, A; Steinhilber, D; Stark, H; Hofmann, B
  • Synthesis and biological evaluation of some thiazolylpyrazole derivatives as dual anti-inflammatory antimicrobial agents
    Bekhit, AA; Fahmy, HT; Rostom, SA; Bekhit, AE-DA
  • Zileuton: clinical implications of 5-lipoxygenase inhibition in severe airway disease
    Berger, W; Chandt, M; Cairns, C
  • Metabolism of leukotriene C4 in γ-glutamyl transpeptidase-deficient mice
    Carter, BZ; Wiseman, AL; Orkiszewski, R; Ballard, KD; Ou, C-N; Lieberman, MW
  • Synthesis and anti-inflammatory activity of some novel biphenyl-4-carboxylic acid 5-(arylidene)-2-(aryl)-4-oxothiazolidin-3-yl amides
    Deep, A; Jain, S; Sharma, PC
  • The pharmacology of arachidonic acid-induced rat paw edema
    DiMartino, M; Campbell, G; Wolff, C; Hanna, N
  • Treatment of asthma with drugs modifying the leukotriene pathway
    Drazen, JM; Israel, E; O’byrne, PM
  • German Patent
    Franke, L; Hofmann, B; Schneider, G; Steinhilber, D
  • The structure of human 5-lipoxygenase
    Gilbert, NC; Bartlett, SG; Waight, MT; Neau, DB; Boeglin, WE; Brash, AR; Newcomer, ME
  • Scaffold-hopping cascade yields potent inhibitors of 5-lipoxygenase
    Hofmann, B; Franke, L; Proschak, E; Tanrikulu, Y; Schneider, P; Steinhilber, D; Schneider, G
  • A class of 5-benzylidene-2-phenylthiazolinones with high potency as direct 5-lipoxygenase inhibitors
    Hofmann, B; Barzen, S; Rödl, CB; Kiehl, A; Borig, J; Živković, A; Stark, H; Schneider, G; Steinhilber, D
  • Molecular pharmacological profile of a novel thiazolinone-based direct and selective 5-lipoxygenase inhibitor
    Hofmann, B; Rödl, C; Kahnt, A; Maier, T; Michel, A; Hoffmann, M; Rau, O; Awwad, K; Pellowska, M; Wurglics, M
  • N-heterocyclic carbene-catalyzed [3 + 4] annulation of enals and alkenyl thiazolones: enantioselective synthesis of thiazole-fused ε-lactones
    Liang, Z-Q; Yi, L; Chen, K-Q; Ye, S
  • The determination of enzyme dissociation constants
    Lineweaver, H; Burk, D
  • Therapeutic role of dual inhibitors of 5-LOX and COX, selective and non-selective non-steroidal anti-inflammatory drugs
    Martel-Pelletier, J; Lajeunesse, D; Reboul, P; Pelletier, J
  • Biosynthesis and metabolism of leukotrienes
    Murphy, RC; Gijón, MA
  • 5-Arylidene-2-imino-4-thiazolidinones: design and synthesis of novel anti-inflammatory agents
    Ottana, R; Maccari, R; Barreca, ML; Bruno, G; Rotondo, A; Rossi, A; Chiricosta, G; Paola, R; Sautebin, L; Cuzzocrea, S
  • 5-Lipoxygenase inhibitors: a review of recent developments and patents
    Pergola, C; Werz, O
  • Enzyme immunoassays of eicosanoids using acetylcholine esterase as label: an alternative to radioimmunoassay
    Pradelles, P; Grassi, J; Maclouf, J
  • 2, 6-difluorophenol as a bioisostere of a carboxylic acid: bioisosteric analogues of γ-aminobutyric acid
    Qiu, J; Stevenson, SH; O’Beirn, MJ; Silverman, RB
  • Exploration of binding site pattern in arachidonic acid metabolizing enzymes, cyclooxygenases and lipoxygenases
    Reddy, KK; Rajan, VKV; Gupta, A; Aparoy, P; Reddanna, P
  • The 5-lipoxygenase inhibitor, zileuton, suppresses prostaglandin biosynthesis by inhibition of arachidonic acid release in macrophages
    Rossi, A; Pergola, C; Koeberle, A; Hoffmann, M; Dehm, F; Bramanti, P; Cuzzocrea, S; Werz, O; Sautebin, L
  • Ueber die Ersetzung der Amid-gruppe durch Chlor, Brom und Cyan in den aromatischen Substanzen
    Sandmeyer, T
  • World Patent
    Schneider, G; Steinhilber, D; Franke, L; Hofmann, B
  • Diaryl-dithiolanes and-isothiazoles: COX-1/COX-2 and 5-LOX-inhibitory, OH scavenging and anti-adhesive activities
    Scholz, M; Ulbrich, HK; Soehnlein, O; Lindbom, L; Mattern, A; Dannhardt, G
  • Design, synthesis, and biological evaluation of some novel indolizine derivatives as dual cyclooxygenase and lipoxygenase inhibitor for anti-inflammatory activity
    Shrivastava, SK; Srivastava, P; Bendresh, R; Tripathi, PN; Tripathi, A
  • Synthesis, anti-inflammatory, analgesic, 5-lipoxygenase (5-LOX) inhibition activities, and molecular docking study of 7-substituted coumarin derivatives
    Srivastava, P; Vyas, VK; Variya, B; Patel, P; Qureshi, G; Ghate, M
  • Distention ulcer as a model for testing of drugs for ulcerogenic side effects
    Szelenyi, I; Thiemer, K
  • Pharmacological investigations of the new antiinflammatory agent 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid. 1st communication: inhibitory effects of rat paw edema
    Tsurumi, K; Kyuki, K; Niwa, M; Kokuba, S; Fujimura, H
  • Zileuton: the first 5-lipoxygenase inhibitor for the treatment of asthma
    Wenzel, SE; Kamada, AK
  • Carrageenin-induced edema in hind paw of the rat as an assay for antiinflammatory drugs
    Winter, CA; Risley, EA; Nuss, GW
  • Leukotriene synthesis is increased by transcriptional up-regulation of 5-lipoxygenase, leukotriene A4 hydrolase, and leukotriene C4 synthase in asthmatic children
    Zaitsu, M; Hamasaki, Y; Matsuo, M; Ichimaru, T; Fujita, I; Ishii, E
  • Studies on thiazolin-4-one: synthesis of some pyrano [2, 3-b]-thiazole derivatives
    Zayed, E; Elbannany, A; Ghozlan, S

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