{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:42:22Z","timestamp":1792806142435,"version":"4.5.0"},"reference-count":74,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T00:00:00Z","timestamp":1626652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["421254\/2018-1"],"award-info":[{"award-number":["421254\/2018-1"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["306798\/2020-4"],"award-info":[{"award-number":["306798\/2020-4"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"name":"State University of Para\u00edba","award":["001\/2021"],"award-info":[{"award-number":["001\/2021"]}],"id":[{"id":"https:\/\/ror.org\/02cm65z11","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Rheumatoid arthritis, arthrosis and gout, among other chronic inflammatory diseases are public health problems and represent major therapeutic challenges. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most prescribed clinical treatments, despite their severe side effects and their exclusive action in improving symptoms, without effectively promoting the cure. However, recent advances in the fields of pharmacology, medicinal chemistry, and chemoinformatics have provided valuable information and opportunities for development of new anti-inflammatory drug candidates. For drug design and discovery, thiophene derivatives are privileged structures. Thiophene-based compounds, like the commercial drugs Tinoridine and Tiaprofenic acid, are known for their anti-inflammatory properties. The present review provides an update on the role of thiophene-based derivatives in inflammation. Studies on mechanisms of action, interactions with receptors (especially against cyclooxygenase (COX) and lipoxygenase (LOX)), and structure-activity relationships are also presented and discussed. The results demonstrate the importance of thiophene-based compounds as privileged structures for the design and discovery of novel anti-inflammatory agents. The studies reveal important structural characteristics. The presence of carboxylic acids, esters, amines, and amides, as well as methyl and methoxy groups, has been frequently described, and highlights the importance of these groups for anti-inflammatory activity and biological target recognition, especially for inhibition of COX and LOX enzymes.<\/jats:p>","DOI":"10.3390\/ph14070692","type":"journal-article","created":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T10:07:37Z","timestamp":1626689257000},"page":"692","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":112,"title":["Thiophene-Based Compounds with Potential Anti-Inflammatory Activity"],"prefix":"10.3390","volume":"14","author":[{"given":"Ryldene Marques Duarte","family":"da Cruz","sequence":"first","affiliation":[{"name":"Post-Graduation Program in Natural and Synthetic Bioactive Products, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3588-833X","authenticated-orcid":false,"given":"Francisco Jaime Bezerra","family":"Mendon\u00e7a-Junior","sequence":"additional","affiliation":[{"name":"Post-Graduation Program in Natural and Synthetic Bioactive Products, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, PB, Brazil"},{"name":"Laboratory of Synthesis and Drug Delivery, State University of Para\u00edba, Jo\u00e3o Pessoa 58071-160, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nat\u00e1lia Barbosa","family":"de M\u00e9lo","sequence":"additional","affiliation":[{"name":"Laboratory of Synthesis and Drug Delivery, State University of Para\u00edba, Jo\u00e3o Pessoa 58071-160, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1866-4107","authenticated-orcid":false,"given":"Luciana","family":"Scotti","sequence":"additional","affiliation":[{"name":"Post-Graduation Program in Natural and Synthetic Bioactive Products, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo Santos Aquino","family":"de Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Laboratory of Synthesis and Drug Delivery, State University of Para\u00edba, Jo\u00e3o Pessoa 58071-160, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinaldo N\u00f3brega","family":"de Almeida","sequence":"additional","affiliation":[{"name":"Post-Graduation Program in Natural and Synthetic Bioactive Products, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo Ol\u00edmpio","family":"de Moura","sequence":"additional","affiliation":[{"name":"Laboratory of Synthesis and Drug Delivery, State University of Para\u00edba, Jo\u00e3o Pessoa 58071-160, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.2174\/1381612824666180327165604","article-title":"Signaling Pathways in Inflammation and Anti-inflammatory Therapies","volume":"24","author":"Yeung","year":"2018","journal-title":"Curr. Pharm. Des."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.matbio.2017.11.010","article-title":"Inflammation and fibrosis","volume":"68\u201369","author":"Mack","year":"2018","journal-title":"Matrix Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.foodchem.2017.09.149","article-title":"Anti-inflammatory properties of edible mushrooms: A review","volume":"243","author":"Muszynska","year":"2018","journal-title":"Food Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"105856","DOI":"10.1016\/j.intimp.2019.105856","article-title":"Design, synthesis and pharmacological evaluation of CVIB, a codrug of carvacrol and ibuprofen as a novel anti-inflammatory agent","volume":"76","author":"Heimfarth","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8536063","DOI":"10.1155\/2018\/8536063","article-title":"Synthesis, Characterization, and Antibacterial and Anti-Inflammatory Activities of New Pyrimidine and Thiophene Derivatives","volume":"2018","author":"Lahsasni","year":"2018","journal-title":"J. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BST20190029","article-title":"Biomarkers of inflammation and the etiology of sepsis","volume":"48","author":"Grondman","year":"2020","journal-title":"Biochem. Soc. Trans."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"154819","DOI":"10.1016\/j.cyto.2019.154819","article-title":"Inflammation in atherosclerosis: A key role for cytokines","volume":"122","author":"Koltsova","year":"2019","journal-title":"Cytokine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1039\/C9MD00276F","article-title":"Evaluation of anti-inflammatory activity and molecular docking study of new azabicyclic isooxazoline acylhydrazone derivatives","volume":"10","author":"Souza","year":"2019","journal-title":"MedChemComm"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/bph.14530","article-title":"Prostaglandin-cytokine crosstalk in chronic inflammation","volume":"176","author":"Yao","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e12970","DOI":"10.1111\/sji.12970","article-title":"An inflammation classification system using cytokine parameters","volume":"93","author":"Roe","year":"2021","journal-title":"Scand. J. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"408","DOI":"10.2174\/1573406413666170209123433","article-title":"Medicinal Chemistry Approaches of Controlling Gastrointestinal Side Effects of Non-Steroidal Anti-Inflammatory Drugs. Endogenous Protective Mechanisms and Drug Design","volume":"13","author":"Tziona","year":"2017","journal-title":"Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1111\/all.13831","article-title":"Cyclooxygenase inhibition in mice heightens adaptive- and innate-type responses against inhaled protease allergen and IL-33","volume":"74","author":"Maruyama","year":"2019","journal-title":"Allergy"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/j.bmc.2016.01.009","article-title":"Design, synthesis and biological evaluation of novel analgesic agents targeting both cyclooxygenase and TRPV1","volume":"26","author":"Yan","year":"2016","journal-title":"Bioorg. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"891","DOI":"10.12688\/f1000research.18338.1","article-title":"A refinement to the formalin test in mice","volume":"8","author":"Lopes","year":"2019","journal-title":"F1000Research"},{"key":"ref_15","first-page":"e201805020","article-title":"Hemorragia digestive y prescripci\u00f3n potencialmente inadecuada de AINEs en mayores de 65 a\u00f1os [Gastrointestinal bleeding and potentially inappropriate medication by NSAIDs]","volume":"92","year":"2018","journal-title":"Rev. Esp. Salud Publica"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1039\/C8MD00457A","article-title":"Rationally synthesized soumarin based pyrazolines ameliorate carrageenan induced inflammation through COX-2\/pro-inflammatory cytokine inhibition","volume":"10","author":"Chandel","year":"2019","journal-title":"Medchemcomm"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/978-1-4939-8549-4_5","article-title":"Markers of Inflammation","volume":"1803","author":"Germolec","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1016\/j.ajpath.2020.06.010","article-title":"Eicosanoids: The Overlooked Storm in Coronavirus Disease 2019 (COVID-19)?","volume":"190","author":"Hammock","year":"2020","journal-title":"Am. J. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1161\/STROKEAHA.119.024157","article-title":"Inflammation, Autoimmunity, Infection, and Stroke: Epidemiology and Lessons from Therapeutic Intervention","volume":"51","author":"Parikh","year":"2020","journal-title":"Stroke"},{"key":"ref_20","first-page":"176","article-title":"Prevalence of chronic pain in Brazil: A descriptive study","volume":"1","author":"Vasconcelos","year":"2018","journal-title":"Br. J. Pain"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Salom\u00e9, D.D.C., Cordeiro, N.M., Val\u00e9rio, T.S., Santos, D.A., Alves, P.B., Alviano, C.S., Moreno, D.S.A., and Fernandes, P.D. (2020). Aristolochia trilobata: Identification of the Anti-inflammatory and Antinociceptive Effects. Biomedicines, 8.","DOI":"10.3390\/biomedicines8050111"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Oz, H.S. (2017). Chronic Inflammatory Diseases and Green Tea Polyphenols. Nutrients, 9.","DOI":"10.3390\/nu9060660"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"112438","DOI":"10.1016\/j.ejmech.2020.112438","article-title":"Recent advancements in the development of heterocyclic anti-inflammatory agents","volume":"200","author":"Sharma","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/s13065-018-0511-5","article-title":"Therapeutic importance of synthetic thiophene","volume":"12","author":"Shah","year":"2018","journal-title":"Chem. Cent. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1016\/j.ejmech.2017.07.038","article-title":"An overview of benzo[b]thiophene-based medicinal chemistry","volume":"138","author":"Keri","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e05520","DOI":"10.1016\/j.heliyon.2020.e05520","article-title":"RMD86, a thiophene derivative, promotes antinociceptive and antipyretic activities in mice","volume":"6","author":"Braga","year":"2020","journal-title":"Heliyon"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.ejmech.2017.09.039","article-title":"2-Aminothiophene scaffolds: Diverse biological and pharmacological attributes in medicinal chemistry","volume":"140","author":"Bozorov","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lisboa, T., Silva, D., Duarte, S., Ferreira, R., Andrade, C., Lopes, A.L., Ribeiro, J., Farias, D., Moura, R., and Reis, M. (2019). Toxicity and Antitumor Activity of a Thiophene-Acridine Hybrid. Molecules, 25.","DOI":"10.3390\/molecules25010064"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"95","DOI":"10.22159\/ajpcr.2017.v10i7.18290","article-title":"Synthesis, antioxidant and anti-inflammatory activities of ethyl 2-(2-cyano-3-(substituted phenyl)acrylamido)-4,5-dimethylthiophene-3-carboxylates","volume":"10","author":"Madhavi","year":"2017","journal-title":"Asian J. Pharm. Clin. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1002\/jms.3640","article-title":"Rapid structural characterization of in vivo and in vitro metabolites os tinoridine using UHPLC-QTOF-MS\/MS and in silico toxicological screening of its metabolites","volume":"50","author":"Kalariya","year":"2015","journal-title":"J. Mass Spectrom."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7536803","DOI":"10.1155\/2019\/7536803","article-title":"The 5-Lipoxygenase Inhibitor Zileuton Protects Pressure Overload-Induced Cardiac Remodeling via Activating PPAR\u03b1","volume":"2019","author":"Wu","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_32","first-page":"e036748","article-title":"Comparative efficacy of traditional non-selective NSAIDs and selective cyclo-oxygenase-2 inhibitors in patients with acute gout: A systematic review and meta-analysis","volume":"10","author":"Li","year":"2020","journal-title":"BJM Open"},{"key":"ref_33","first-page":"6784","article-title":"Hypersensitivity Reactions to Non-Steroidal Anti-Inflammatory Drugs","volume":"45","author":"Dona","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"113774","DOI":"10.1016\/j.bcp.2019.113774","article-title":"Inhibition of lipolysis: A novel explanation for the hypothermic actions of acetaminophen in non-febrile rodents","volume":"172","author":"Bashir","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/1440-1681.13392","article-title":"Paracetamol\u2014An old drug with new mechanisms of action","volume":"48","author":"Przybyla","year":"2021","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1001\/jamainternmed.2020.2821","article-title":"Nonsteroidal Anti-inflammatory Drugs vs. Cognitive Behavioral Therapy for Arthritis Pain: A Randomized Withdrawal Trial","volume":"180","author":"Fraenkel","year":"2020","journal-title":"JAMA Intern. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1097\/MOG.0000000000000427","article-title":"NSAIDs and the small bowel","volume":"34","author":"Tai","year":"2018","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_38","first-page":"349","article-title":"Cardiovascular risk of non-steroidal anti-inflammatory drugs","volume":"78","author":"Prozzi","year":"2018","journal-title":"Medicina"},{"key":"ref_39","first-page":"1","article-title":"Cyclo-oxygenase-2 expression is associated with mean standardised uptake value on 18F-Fluorodeoxyglucose positron emission tomography in oesophageal adenocarcinoma","volume":"1099","author":"Foley","year":"2019","journal-title":"Br. J. Radiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/jcpt.12484","article-title":"Non-steroidal anti-inflammatory drug-induced cardiovascular adverse events: A meta-analysis","volume":"42","author":"Gunter","year":"2017","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_41","first-page":"727","article-title":"Correlation of LOX-5 and COX-2 expression with inflammatory pathology and clinical features of adenomyosis","volume":"19","author":"Li","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_42","first-page":"36","article-title":"Inflammatory mediators of neuropathic pain","volume":"17","author":"Cohen","year":"2016","journal-title":"Rev. Dor"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"371","DOI":"10.3109\/14756366.2014.940932","article-title":"Synthesis of new isooxazoline derivatives from harmine and evaluation of their anti-Alzheimer, anti-cancer and anti-inflammatory activities","volume":"30","author":"Filali","year":"2015","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Chiasson, A.I., Robichaud, S., Ndongou Moutombi, F.J., H\u00e9bert, M.P.A., Mbarik, M., Surette, M.E., and Touaibia, M. (2020). New Zileuton-Hydroxycinnamic Acid Hybrids: Synthesis and Structure-Activity Relationship towards 5-Lipoxygenase Inhibition. Molecules, 25.","DOI":"10.3390\/molecules25204686"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3109\/14756366.2014.913035","article-title":"Implication of novel management of asthma","volume":"30","author":"Patil","year":"2015","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1007\/s10741-018-9716-x","article-title":"Role of cytokines and inflammation in heart function during health and disease","volume":"23","author":"Bartekova","year":"2018","journal-title":"Heart Fail. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.jacbts.2018.08.006","article-title":"Characterization of the myocardial inflammatory response in acute stress-induced (Takotsubo) cardiomyopathy","volume":"3","author":"Wilson","year":"2018","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.immuni.2019.03.020","article-title":"IL-10 Family Cytokines IL-10 and IL-22: From Basic Science to Clinical Translation","volume":"50","author":"Ouyang","year":"2019","journal-title":"Immunity"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Hu, J., Wang, G., Liu, X., Zhou, L., Jiang, M., and Yang, L. (2013). Polo-like kinase 1 (PLK1) is involved in toll-like receptor (TLR)-mediated TNF-\u03b1 production in monocytic THP-A cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0078832"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.matt.2020.05.017","article-title":"Calming Cytokine Storm in Pneumonia by Targeted Delivery of TPCA-1 Using Platelet-Derived Extracellular Vesicles","volume":"3","author":"Ma","year":"2020","journal-title":"Matter"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/j.ejmech.2016.07.010","article-title":"Design of a novel thiophene inhibitor of 15-lipoxygenase-1 with both anti-inflammatory and neuroprotective properties","volume":"122","author":"Eleftheriadis","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"101701","DOI":"10.1016\/j.pdpdt.2020.101701","article-title":"Photo induced anti-inflammatory activities of a Thiophene substituted subphthalocyanine derivative","volume":"30","author":"Yuzer","year":"2020","journal-title":"Photodiagnosis Photodyn. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"103484","DOI":"10.1016\/j.bioorg.2019.103484","article-title":"Synthesis and discovery of pyrazolo-pyridine analogs as inflammation medications through pro- and anti-inflammatory cytokine and COX-2 inhibition assessments","volume":"94","author":"Manikandan","year":"2020","journal-title":"Bioorg. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1124\/mol.111.074039","article-title":"High-affinity peroxisome proliferator-activated receptor \u03b2\/\u03b4-specific ligands with pure antagonistic or inverse agonistic properties","volume":"80","author":"Naruhn","year":"2011","journal-title":"Mol. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s00011-015-0814-0","article-title":"Systemic changes following carrageenan-induced paw inflammation in rats","volume":"64","author":"Vazquez","year":"2015","journal-title":"Inflamm. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.bioorg.2019.01.031","article-title":"COX-1\/COX-2 inhibition assays and histopathological study of the new designed anti-inflammatory agent with a pyrazolopyrimidine core","volume":"86","author":"Abdelall","year":"2019","journal-title":"Bioorg. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/ni.3049","article-title":"The immunology of asthma","volume":"16","author":"Lambrecht","year":"2015","journal-title":"Nat. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/978-1-4939-8994-2_28","article-title":"OVA-Induced Allergic Airway Inflammation Mouse Model","volume":"1916","author":"Casaro","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.bioorg.2018.06.023","article-title":"Design and Amberlyst-15 mediated synthesis of novel thianyl-pyrazole carboxamides that potently inhibit Phospholipase A2 by binding to an allosteric site on the enzyme","volume":"80","author":"Kumar","year":"2018","journal-title":"Bioorg. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.saa.2015.03.070","article-title":"Design, synthesis, characterization, quantum-chemical calculations and anti-inflammatory activity of novel series of thiophene derivatives","volume":"147","author":"Helal","year":"2015","journal-title":"Spectrochim. Acta A Mol. Biomol. Spectrosc."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"102","DOI":"10.2174\/1871523017666180910105609","article-title":"Synthesis and Biological Evaluation of Novel 2-(4-acetyl-3-methyl-5-(arylamino)thiophen-2-yl)-3-arylquinazolin-4(3H)-one Derivatives as Potential Anti-inflammatory and Antioxidant Agents","volume":"17","author":"Chaudhari","year":"2018","journal-title":"Atiinflamm. Antiallergy Agents Med. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"111562","DOI":"10.1016\/j.ejmech.2019.111562","article-title":"Synthesis and evaluation of 2,5-furan, 2,5-thiophene and 3,4-thiophene-based derivatives as CXCR4 inhibitors","volume":"181","author":"Gaines","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1007\/s10517-013-2078-4","article-title":"Effect of IKK-2 inhibitor on local Th1 and Th2 type inflammation","volume":"155","author":"Ligacheva","year":"2013","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.bioorg.2017.03.012","article-title":"New hybrid molecules combining benzothyophene or benzofuran with rhodanine as dual COX-1\/2 and 5-LOX inhibitors: Synthesis, biological evaluation and docking study","volume":"72","author":"Hazzaa","year":"2017","journal-title":"Bioorg. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"998","DOI":"10.2174\/1568026618666180813152921","article-title":"Structure-Based Drug Design Strategies and Challenges","volume":"18","author":"Wang","year":"2018","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4033","DOI":"10.1021\/acs.jmedchem.6b00511","article-title":"Advances in Computational Medicinal Chemistry: A Reflection on the Evolution of the Field and Perspective Going Forward","volume":"59","author":"Shoichet","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/978-1-4939-6634-9_5","article-title":"Computer-Aided Drug Design Methods","volume":"1520","author":"Yu","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"107348","DOI":"10.1016\/j.compbiolchem.2020.107348","article-title":"Design, molecular docking analysis of an anti-inflammatory drug, computational analysis and intermolecular interactions energy studies of 1-benzothiophene-2-carboxylic acid","volume":"88","author":"Sagaama","year":"2020","journal-title":"Comput. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.saa.2015.01.025","article-title":"Spectroscopic investigations, molecular interactions, and molecular docking studies on the potential inhibitor \u201cthiophene-2-carboxylicacid\u201d","volume":"141","author":"Karthick","year":"2015","journal-title":"Spectrochim. Acta A Mol. Biomol. Spectrosc."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"55","DOI":"10.3998\/ark.5550190.0012.a05","article-title":"Synthesis and docking studies of thiophene scaffolds in COX-2","volume":"2011","author":"Singh","year":"2011","journal-title":"Arkivoc"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e04125","DOI":"10.1016\/j.heliyon.2020.e04125","article-title":"Quantum mechanics and 3D-QSAR studies on thienopyridine analogues: Inhibitors of IKK\u03b2","volume":"6","author":"Khan","year":"2020","journal-title":"Heliyon"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.bioorg.2019.02.036","article-title":"Pyrazoles containing thiophene, thienopyrimidine and thienotriazolopyrimidine as COX-2 selective inhibitors: Design, synthesis, in vivo anti-inflammatory activity, docking and in silico chemoinformatic studies","volume":"85","author":"AboulWafa","year":"2019","journal-title":"Bioorg. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1016\/j.bmcl.2017.02.076","article-title":"Novel 2-phenyl-4,5,6,7-tetrahydro[b]benzothiophene analogues as selective COX-2 inhibitors: Design, synthesis, anti-inflammatory evaluation, and molecular docking studies","volume":"27","author":"Khatri","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"126934","DOI":"10.1016\/j.molstruc.2019.126934","article-title":"Molecular docking, structural characterization, DFT and cytotoxicity studies of metal (II) Schiff base complexes derived from thiophene-2-carboxaldehyde and L-histidine","volume":"1198","author":"John","year":"2019","journal-title":"J. Mol. Struct."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/14\/7\/692\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:31:44Z","timestamp":1760164304000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/14\/7\/692"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,19]]},"references-count":74,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["ph14070692"],"URL":"https:\/\/doi.org\/10.3390\/ph14070692","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,19]]}}}