Exploring New Imines as Anti-Inflammatory COX and 5-LOX Inhibitors with an Improved Pharmacokinetic Profile

References

• Fiorucci S , Meli R , Bucci M , Cirino G . Dual inhibitors of cyclooxygenase and 5-lipoxygenase. A new avenue in anti-inflammatory therapy? Biochem. Pharmacol. 62(11), 1433–1438 (2001).
   PubMed Web of Science ®Google Scholar
• Zeilhofer HU . Prostanoids in nociception and pain. Biochem. Pharmacol. 73(2), 165–174 (2007).
   PubMed Web of Science ®Google Scholar
• Miao X-P , Li J-S , Ouyang Q , Hu R-W , Zhang Y , Li H-Y . Tolerability of selective cyclooxygenase 2 inhibitors used for the treatment of rheumatological manifestations of inflammatory bowel disease. Cochrane Database Syst. Rev. (10), CD007744 (2014).
   PubMed Web of Science ®Google Scholar
• Burnett B , Levy RM . 5-lipoxygenase metabolic contributions to NSAID-induced organ toxicity. Adv. Ther. 29(2), 79–98 (2012).
   PubMed Web of Science ®Google Scholar
• Morphy R , Rankovic Z . Medicinal chemistry approaches for multitarget drugs. Burger’s Med. Chem. Drug Discov. 249–274 (2010).
   Google Scholar
• Charlier C , Michaux C . Dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) as a new strategy to provide safer non-steroidal anti-inflammatory drugs. Eur. J. Med. Chem. 38(7–8), 645–659 (2003).
   PubMed Web of Science ®Google Scholar
• Ding C , Cicuttini F . Licofelone (Merckle) (2003). https://figshare.utas.edu.au/articles/journal_contribution/Licofelone_Merckle_/23228078
   Google Scholar
• Nisha , Singh S , Sharma N , Chandra R . The indole nucleus as a selective COX-2 inhibitor and anti-inflammatory agent (2011–2022). Org. Chem. Front. 9(13), 3624–3639 (2022).
   Web of Science ®Google Scholar
• de Marigorta EM , Santos JM de L , Ochoa de Retana AM , Vicario J , Palacios F . Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams. Beilstein J. Org. Chem. 15, 1065–1085 (2019).
   PubMed Web of Science ®Google Scholar
• Sharma S , Monga Y , Gupta A , Singh S . 2-Oxindole and related heterocycles: synthetic methodologies for their natural products and related derivatives. RSC Adv. 13(21), 14249–14267 (2023).
   PubMed Web of Science ®Google Scholar
• Mitchell JA , Larkin S , Williams TJ . Cyclooxygenase-2: regulation and relevance in inflammation. Biochem. Pharmacol. 50(10), 1535–1542 (1995).
   PubMed Web of Science ®Google Scholar
• Abdellatif K , Elsaady M , Amin N , Hefny A . Design, synthesis and biological evaluation of some novel indole derivatives as selective COX-2 inhibitors. J. Appl. Pharm. Sci. 7(8), 69–77 (2017).
   Google Scholar
• Nelson SD . Structure toxicity relationships – how useful are they in predicting toxicities of new drugs? Adv. Exp. Med. Biol. 500, 33–43 (2001).
   PubMed Web of Science ®Google Scholar
• Fouda HG , Avery MJ , Dalvie D , Falkner FC , Melvin LS , Ronfeld RA . Disposition and metabolism of tenidap in the rat. PubMed 25(2), 140–148 (1997).
   Google Scholar
• Lai Y , Ma L , Huang W et al. Synthesis and biological evaluation of 3-[4-(amino/methylsulfonyl) phenyl] methylene-indolin-2-one derivatives as novel COX-1/2 and 5-LOX inhibitors. Bioorg. Med. Chem. Lett. 20(24), 7349–7353 (2010).
   PubMed Web of Science ®Google Scholar
• Lamie PF , Ali WAM , Bazgier V , Rárová L . Novel N-substituted indole Schiff bases as dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase enzymes: synthesis, biological activities in vitro and docking study. Eur. J. Med. Chem. 123, 803–813 (2016).
   PubMed Web of Science ®Google Scholar
• Prasher P . Identification of triazole bridged amino acids appended indoles as dual inhibitors of 5-LOX and COX-2 enzymes. Int. J. Chem. Tech. Res. 9(7), 453–465 (2016).
   Google Scholar
• Masimirembwa CM , Bredberg U , Andersson TB . Metabolic stability for drug discovery and development. Clin. Pharmacokinet. 42(6), 515–528 (2003).
   PubMed Web of Science ®Google Scholar
• Starkov SP , Polyanskaya NL . Synthesis, structure, and reactions of chelates of 2′-(difluoroboroxy)-3′,4′-benzochalcone and its 5′-alkyl-sustituted derivatives. Chemischer. Informationsdienst. 9(8), (1978). doi.10.1002/chin.197808250
   Google Scholar
• Kaur J , Bhardwaj A , Huang Z , Knaus EE . N-1 and C-3 substituted indole Schiff bases as selective COX-2 inhibitors: synthesis and biological evaluation. Bioorganic Med. Chem. Lett. 22(6), 2154–2159 (2012).
   PubMed Web of Science ®Google Scholar
• Mandour A , El-Sawy E , Shaker K , Mustafa M . Synthesis, anti-inflammatory, analgesic and anticonvulsant activities of 1,8-dihydro-1-ary1-8-alkyl pyrazolo(3,4-b) indoles. Acta Pharmaceut. 60(1), 73–88 (2010).
   PubMed Web of Science ®Google Scholar
• Cornforth JW , Cornforth RH , Dalgliesh CE , Neuberger A . dl-β-3-Oxindolylalanine (dl-hydroxytryptophan). Synthesis Biochem. J. 48(5), 591–597 (1951).
   PubMed Web of Science ®Google Scholar
• Kaïm LE , Gautier L , Grimaud L , Harwood LM , Michaut V . The Mannich reaction of hydrazones: improved reactivity under solvent-free conditions. Green Chem. 5(4), 477–479 (2003).
   Web of Science ®Google Scholar
• Xu S , Hermanson DJ , Banerjee S . Crystal structure of ovine cyclooxygenase-1 complex with meloxicam RCSB PDB: Protein Data Bank (2014). www.rcsb.org/structure/4o1z
   Google Scholar
• Kiefer JR , Kurumbail RG , Stallings WC . Structure of celecoxib bound at the COX-2 active site RCSB PDB: Protein Data Bank (2010). www.rcsb.org/structure/3ln1
   Google Scholar
• Newcomer ME , Gilbert NC , Bartlett SG . Stable-5-lipoxygenase RCSB PDB: Protein Data Bank (2011). www.rcsb.org/structure/3o8y
   Google Scholar
• Bell EW , Zhang Y . DockRMSD: an open-source tool for atom mapping and RMSD calculation of symmetric molecules through graph isomorphism. J. Cheminformat. 11(1), (2019).
   PubMedGoogle Scholar
• European Medicines Agency . Committee for Medicinal Products for Human Use (CHMP) Guideline on bioanalytical method validation. www.ema.europa.eu/en/documents/scientific-guideline/guideline-bioanalytical-method-validation_en.pdf
   Google Scholar
• Zhang M , Mulholland N , Seville A et al. First discovery of pimprinine derivatives and analogs as novel potential herbicidal, insecticidal and nematicidal agents. Tetrahedron 79, 131835 (2021).
   Web of Science ®Google Scholar
• Budovsk M , Piltov MB , Tischlerov V , Moji J . Spirocyclization reactions and antiproliferative activity of indole phytoalexins 1-methoxybrassinin and its 1-substituted derivatives. Arkivoc 2016(6), 198–234 (2017).
   Google Scholar
• Winter CA , Risley EA , Nuss GW . Carrageenin-induced edema in hind paw of the rat as an assay for antiinflammatory drugs. EBM 111(3), 544–547 (1962).
   PubMed Web of Science ®Google Scholar
• Collier HOJ , Dinneen LC , Johnson CA , Schneider C . The abdominal constriction response and its suppression by analgesic drugs in the mouse. Br. J. Pharmacol. Chemother. 32(2), 295–310 (1968).
   PubMed Web of Science ®Google Scholar
• Finney DJ . Statistical method in biological assay. 2. Aufl. Charles Griffin & Cc. Ltd., London 1964. XIX + 668 S., Preis 105 s. Biometrische Zeitschrift. 7(3), 206 (1965).
   Google Scholar
• Robert A , Je N , Phillips JP . Effect of prostaglandin E1 on gastric secretion and ulcer formation in the rat. Gastroenterology 55(4), 481–487 (1968).
   PubMed Web of Science ®Google Scholar
• Meshali M , El-Sabbagh H , Foda A . Effect of encapsulation of flufenamic acid with acrylic resins on its bioavailability and gastric ulcerogenic activity in rats. Acta Pharm. Technol. 29, 217–219 (1983).
   Google Scholar
• Bancroft JD , Stevans A , Turner DR . Theory and Practice of Histological Techniques (Fourth Ed.). Churchill Livingstone, Edinburgh, London, Melbourne, New York (1996).
   Google Scholar
• Kim TH , Jeon EJ , Cheung DY et al. Gastroprotective effects of grape seed proanthocyanidin extracts against nonsteroid anti-inflammatory drug-induced gastric injury in rats. Gut Liver 7(3), 282–289 (2013).
   PubMed Web of Science ®Google Scholar
• Redzicka A , Szczukowski Ł , Kochel A , Wiatrak B , Gębczak K , Czyżnikowska Ż . COX-1/COX-2 inhibition activities and molecular docking study of newly designed and synthesized pyrrolo[3,4-c] pyrrole Mannich bases. Bioorg. Med. Chem. 27(17), 3918–3928 (2019).
   PubMed Web of Science ®Google Scholar
• Kiefer JR , Pawlitz JL , Moreland KT et al. Structural insights into the stereochemistry of the cyclooxygenase reaction. Nature 405(6782), 97–101 (2000).
   PubMed Web of Science ®Google Scholar
• Kanamori K , Roberts JD . Nitrogen-15 nuclear magnetic resonance study of benzenesulfonamide and cyanate binding to carbonic anhydrase. Biochemistry 22(11), 2658–2664 (1983).
   PubMed Web of Science ®Google Scholar
• Sisa M , Dvorakova M , Temml V , Jarosova V , Vaněk T , Landa P . Synthesis, inhibitory activity and in silico docking of dual COX/5-LOX inhibitors with quinone and resorcinol core. Eur. J. Med. Chem. 204, 112620 (2020).
   PubMed Web of Science ®Google Scholar
• Daina A , Michielin O , Zoete V . SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep. 7(1), 42717 (2017).
   PubMedGoogle Scholar
• Lipinski CA , Lombardo F , Dominy BW , Feeney PJ . Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Delivery Rev. 23(1–3), 3–25 (1997).
   Web of Science ®Google Scholar
• Lipinski CA . Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov. Today: Technol. 1(4), 337–341 (2004).
   PubMedGoogle Scholar
• Veber DF , Johnson SR , Cheng H-Y , Smith BR , Ward KW , Kopple KD . Molecular properties that influence the oral bioavailability of drug candidates. J. Med. Chem. 45(12), 2615–2623 (2002).
   PubMed Web of Science ®Google Scholar
• Delaney JS . ESOL: estimating aqueous solubility directly from molecular structure. J. Chem. Inf. Comput. Sci. 44(3), 1000–1005 (2004).
   PubMedGoogle Scholar
• Lin JH , Yamazaki M . Role of P-glycoprotein in pharmacokinetics. Clin. Pharmacokinet. 42(1), 59–98 (2003).
   PubMed Web of Science ®Google Scholar
• Egan WJ , Merz KM , Baldwin JJ . Prediction of Drug Absorption using multivariate statistics. J. Med. Chem. 43(21), 3867–3877 (2000).
   PubMed Web of Science ®Google Scholar
• Martin YC . A bioavailability score. J. Med. Chem. 48(9), 3164–3170 (2005).
   PubMed Web of Science ®Google Scholar