Synthesis, molecular docking, analgesic, anti-inflammatory, and ulcerogenic evaluation of thiophene-pyrazole candidates as COX, 5-LOX, and TNF-α inhibitors

Abd El-Karim SS et al (2021) Design, synthesis and molecular docking of new pyrazole-thiazolidinones as potent anti-inflammatory and analgesic agents with TNF-α inhibitory activity. Bioorg Chem 111(January):104827. https://doi.org/10.1016/j.bioorg.2021.104827 Abdelgawad MA et al (2018) Design, synthesis, analgesic, anti-inflammatory activity of novel pyrazolones possessing aminosulfonyl pharmacophore as inhibitors of COX-2/5-LOX enzymes: Histopathological and docking studies. Bioorgan Chem 78:103–114. https://doi.org/10.1016/j.bioorg.2018.03.011 Ahmed AHH et al (2022) Design, synthesis, and molecular docking of novel pyrazole-chalcone analogs of lonazolac as 5-LOX, iNOS and tubulin polymerization inhibitors with potential anticancer and anti-inflammatory activities. Bioorganic Chemistry 129:106171. https://doi.org/10.1016/j.bioorg.2022.106171 Alanazi AM et al (2015) Structure-based design of phthalimide derivatives as potential cyclooxygenase-2 (COX-2) inhibitors: anti-inflammatory and analgesic activities. Eur J Med Chem 92:115–123. https://doi.org/10.1016/j.ejmech.2014.12.039 Alfi AA et al (2022) Molecular modeling and docking studies of new antioxidant pyrazole-thiazole hybrids. J Mol Struct 1267:133582. https://doi.org/10.1016/j.molstruc.2022.133582 Arunkumar S et al (2009) Synthesis and Anti-inflammatory Activity of Some Novel Pyrazole Derivatives of Gallic Acid. E J Chem 6:128586. https://doi.org/10.1155/2009/128586 Bekhit AA et al (2022) Investigation of the anti-inflammatory and analgesic activities of promising pyrazole derivative. Eur J Pharm Sci 168:106080. https://doi.org/10.1016/J.EJPS.2021.106080 Blobaum AL, Marnett LJ (2007) Structural and Functional basis of cyclooxygenase inhibition. J Med Chem 50(7):1425–1441. https://doi.org/10.1021/jm0613166 Chaaban I et al (2018) Synthesis, anti-inflammatory screening, molecular docking, and COX-1,2/-5-LOX inhibition profile of some novel quinoline derivatives. Bioorg Chem 78:220–235. https://doi.org/10.1016/j.bioorg.2018.03.023 Collier HO et al (1968) The abdominal constriction response and its suppression by analgesic drugs in the mouse. Br J Pharmacol Chemother 32(2):295–310. https://doi.org/10.1111/j.1476-5381.1968.tb00973.x da Cruz RMD et al (2021) Thiophene-based compounds with potential anti-inflammatory activity. Pharmaceuticals 14(7):692. https://doi.org/10.3390/ph14070692 El-Miligy MMM et al (2017) New hybrid molecules combining benzothiophene or benzofuran with rhodanine as dual COX-1/2 and 5-LOX inhibitors: Synthesis, biological evaluation and docking study. Bioorg Chem 72:102–115. https://doi.org/10.1016/j.bioorg.2017.03.012 Gurupadaswamy HD et al (2022) Competent synthesis of biaryl analogs via asymmetric Suzuki-Miyaura cross-coupling for the development of anti-inflammatory and analgesic agents. J Iran Chem Soc 19(6):2421–2436. https://doi.org/10.1007/s13738-021-02460-0 Jyothi M et al (2022) Microwave-assisted synthesis, characterization, docking studies and molecular dynamic of some novel phenyl thiazole analogs as xanthine oxidase inhibitor. J Iran Chem Soc 19(9):3919–3933. https://doi.org/10.1007/s13738-022-02574-z Kang D et al (2020) Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs. Acta Pharm Sin B 10(5):878–894. https://doi.org/10.1016/j.apsb.2019.08.013 Khadri MJN, Prashanth T et al (2022) Synthesis, analgesic, anti-inflammatory, COX/5-LOX inhibition, ulcerogenic evaluation, and docking study of benzimidazole bearing indole and benzophenone analogs. J Mol Struct 1259:132741. https://doi.org/10.1016/j.molstruc.2022.132741 Khadri MJN, Khamees HA et al (2022) Synthesis, analgesic, anti-inflammatory, ulcerogenic evaluation, and docking study of (benzoylphenoxy)-N-{5-[2-methylphenyl-6-chlorobenzoxazole]} acetamides as COX/5-LOX inhibitor. J Mol Struct 1272:134240. https://doi.org/10.1016/j.molstruc.2022.134240 Khadri MJN et al (2023) Synthesis and docking studies of pyrazole-benzamide-benzothiazole conjugates as xanthine oxidase inhibitor candidates. Journal of Molecular Structure 1290:135937. https://doi.org/10.1016/j.molstruc.2023.135937 Küçükgüzel G, ŞenkardeŞ S (2015) Recent advances in bioactive pyrazoles. Eur J Med Chem 97(1):786–815. https://doi.org/10.1016/j.ejmech.2014.11.059 Kuppusamy R et al (2022) ‘Benzo[b]thiophene-2-carboxamides as novel opioid receptor agonists with potent analgesic effect and reduced constipation. Eur J Med Chem 243:114728. https://doi.org/10.1016/j.ejmech.2022.114728 Malani K et al (2016) Synthesis, characterization and in silico designing of diethyl-3-methyl-5-(6-methyl-2-thioxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxamido) thiophene-2,4-dicarboxylate derivative as anti-proliferative and anti-microbial agents. Bioorg Chem 68:265–274. https://doi.org/10.1016/j.bioorg.2016.09.001 Mantzanidou M, Pontiki E, Hadjipavlou-Litina D (2021) ‘Pyrazoles and pyrazolines as anti-inflammatory agents. Molecules (Basel, Switzerland) 26(11):3439. https://doi.org/10.3390/molecules26113439 Martiz RM et al (2022) Defining the role of isoeugenol from ocimum tenuiflorum against diabetes mellitus-linked alzheimer & disease through network pharmacology and computational methods. Molecules. https://doi.org/10.3390/molecules27082398 Martiz Reshma Mary, Patil SM, Ramu R et al (2022) Discovery of novel benzophenone integrated derivatives as anti-Alzheimer’s agents targeting presenilin-1 and presenilin-2 inhibition: a computational approach. PLoS ONE 17(4):e0265022. https://doi.org/10.1371/journal.pone.0265022 Martiz RM, Patil SM, Thirumalapura Hombegowda D et al (2022) Phyto-Computational intervention of diabetes mellitus at multiple stages using isoeugenol from ocimum tenuiflorum: a combination of pharmacokinetics and molecular modelling approaches. Molecules 27(19):6222. https://doi.org/10.3390/molecules27196222 Megally Abdo NY, Samir EM, Mohareb RM (2020) Synthesis and evaluation of novel 4H-pyrazole and thiophene derivatives derived from chalcone as potential anti-proliferative agents, Pim-1 kinase inhibitors, and pains. J Heterocycl Chem 57(4):1993–2009. https://doi.org/10.1002/jhet.3928 Narayanan SE et al (2021) Design, synthesis and biological evaluation of substituted pyrazoles endowed with brominated 4-methyl 7-hydroxy coumarin as new scaffolds against Alzheimer’s disease. Future J Pharm Sci 7(1):161. https://doi.org/10.1186/s43094-021-00278-4 Nayak SG, Poojary B, Kamat V (2020) Novel pyrazole-clubbed thiophene derivatives via Gewald synthesis as antibacterial and anti-inflammatory agents. Archiv der Pharmazie 353(12):2000103. https://doi.org/10.1002/ardp.202000103 Obu QS et al (2021) Synthesis, spectra (FT-IR, NMR) investigations, DFT study, in silico ADMET and molecular docking analysis of 2-amino-4-(4-aminophenyl)thiophene-3-carbonitrile as a potential anti-tubercular agent. J Mol Struct 1244:130880. https://doi.org/10.1016/j.molstruc.2021.130880 Omar YM, Abdu-Allah HHM, Abdel-Moty SG (2018) Synthesis, biological evaluation and docking study of 1,3,4-thiadiazole-thiazolidinone hybrids as anti-inflammatory agents with dual inhibition of COX-2 and 15-LOX. Bioorg Chem 80:461–471. https://doi.org/10.1016/j.bioorg.2018.06.036 Patil SM et al (2021) Comparative molecular docking and simulation analysis of molnupiravir and remdesivir with SARS-CoV-2 RNA dependent RNA polymerase (RdRp). Bioinformation 17(11):932–939. https://doi.org/10.6026/97320630017932 Patil SM, Martiz Reshma M et al (2022) Discovery of novel coumarin derivatives as potential dual inhibitors against α-glucosidase and α-amylase for the management of post-prandial hyperglycemia via molecular modelling approaches. Molecules. https://doi.org/10.3390/molecules27123888 Patil SM, Martiz Reshma Mary et al (2022) Evaluation of flavonoids from banana pseudostem and flower (quercetin and catechin) as potent inhibitors of α-glucosidase: an in silico perspective. J Biomol Struct Dyn 40(23):12491–12505. https://doi.org/10.1080/07391102.2021.1971561 Patil SM, Al-Mutairi KA et al (2022) Pharmacoinformatics based screening discovers swertianolin from Lavandula angustifolia as a novel neuromodulator targeting epilepsy, depression, and anxiety. South Afr J Bot 149:712–730. https://doi.org/10.1016/j.sajb.2022.06.054 Prabhakaran S et al (2022) One-pot three-component synthesis of novel phenyl-pyrano-thiazol-2-one derivatives and their anti-diabetic activity studies. Results in Chemistry 4:100439 Priya D et al (2022) Structural insights into pyrazoles as agents against anti-inflammatory and related disorders. ChemistrySelect 7(5):e202104429. https://doi.org/10.1002/slct.202104429 Puttaswamy N, Rekha ND et al (2018) Anti-inflammatory and antioxidant activity of salicylic acid conjugated dihydropyrazoline analogues. J Appl Pharm Sci 8(2):060–064. https://doi.org/10.7324/JAPS.2018.8209 Puttaswamy N, Malojiao VH et al (2018) Synthesis and amelioration of inflammatory paw edema by novel benzophenone appended oxadiazole derivatives by exhibiting cyclooxygenase-2 antagonist activity. Biomed Pharmacother 103:1446–1455. https://doi.org/10.1016/j.biopha.2018.04.167 Qandeel NA et al (2020) Synthesis, in vivo anti-inflammatory, COX-1/COX-2 and 5-LOX inhibitory activities of new 2,3,4-trisubstituted thiophene derivatives. Bioorgan Chem 102:103890. https://doi.org/10.1016/j.bioorg.2020.103890 Rajput A, Ware CF (2016) ‘Tumor necrosis factor signaling pathways’, Encyclopedia of Cell Biology. Edited by R.A. Bradshaw and P.D.B.T.-E. of C.B. Stahl 3:354–363. https://doi.org/10.1016/B978-0-12-394447-4.30048-7 Serhan CN, Petasis NA (2011) Resolvins and protectins in inflammation resolution. Chem Rev 111(10):5922–5943. https://doi.org/10.1021/cr100396c Shaker AMM et al (2022) Novel 1,3-diaryl pyrazole derivatives bearing methylsulfonyl moiety: design, synthesis, molecular docking and dynamics, with dual activities as anti-inflammatory and anticancer agents through selectively targeting COX-2. Bioorganic Chemistry 129:106143. https://doi.org/10.1016/j.bioorg.2022.106143 Shingare R et al (2022) Docking stimulations and primary assessment of newly synthesized benzene sulfonamide pyrazole oxadiazole derivatives as potential antimicrobial and antitubercular agents. Polycycl Arom Compd 43:1799–1811. https://doi.org/10.1080/10406638.2022.2036771 Shivanna C et al (2022) Synthesis, Characterization, Hirshfeld Surface Analysis, Crystal Structure and Molecular Modeling Studies of 1-(4-(Methoxy(phenyl)methyl)-2-methylphenoxy)butan-2-one Derivative as a Novel α-Glucosidase Inhibitor. Crystals. https://doi.org/10.3390/cryst12070960 Sumi M, Nevaditha NT, Sindhu Kumari B (2023) Synthesis, structural evaluation, antioxidant, DNA cleavage, anticancer activities and molecular docking study of metal complexes of 2-amino thiophene derivative. J Mol Struct 1272:134091. https://doi.org/10.1016/j.molstruc.2022.134091 Wu Z et al (2021) In vivo antiviral activity and disassembly mechanism of novel 1-phenyl-5-amine-4-pyrazole thioether derivatives against Tobacco mosaic virus. Pestic Biochem Physiol 173:104771. https://doi.org/10.1016/j.pestbp.2021.104771 Xie WL et al (1991) ‘Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing. Proc Natl Acad Sci USA 88(7):2692–2696. https://doi.org/10.1073/pnas.88.7.2692 Yan R et al (2021) Synthesis and activity evaluation of some pyrazole-pyrazoline derivatives as dual anti-inflammatory and antimicrobial agents. Polycyclic Aromatic Compounds 42:1–14. https://doi.org/10.1080/10406638.2021.1919156 Youssif BGM et al (2019) Novel aryl carboximidamide and 3-aryl-1,2,4-oxadiazole analogues of naproxen as dual selective COX-2/15-LOX inhibitors: Design, synthesis and docking studies. Bioorganic Chemistry 85:577–584. https://doi.org/10.1016/j.bioorg.2019.02.043 Zabiulla et al (2019) Design, synthesis and molecular docking of benzophenone conjugated with oxadiazole sulphur bridge pyrazole pharmacophores as anti inflammatory and analgesic agents. Bioorganic Chemistry 92(August):103220. https://doi.org/10.1016/j.bioorg.2019.103220