{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:27:06Z","timestamp":1791923226423,"version":"4.3.4"},"reference-count":44,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T00:00:00Z","timestamp":1594857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005328","name":"Female Center for Scientific and Medical Colleges, King Saud University","doi-asserted-by":"publisher","award":["00"],"award-info":[{"award-number":["00"]}],"id":[{"id":"10.13039\/501100005328","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>New pyranocoumarin and coumarin-sulfonamide derivatives were prepared and evaluated for their antioxidant, antimicrobial, and\/or anti-inflammatory activities. Coumarin-sulfonamide compounds 8a\u2013d demonstrated significant antioxidant activity, while 7c,d, 8c,d, and 9c,d exhibited antimicrobial activity equal to or higher than the standard antimicrobials against at least one tested microorganism. Regarding the anti-inflammatory testing, pyranocoumarins 2b, 3a,b and 5c and coumarin-sulfonamide compound 9a showed more potent antiproteinase activity than aspirin in vitro; however, five compounds were as potent as aspirin. The anti-inflammatory activity of the promising compounds was further assessed pharmacologically on formaldehyde-induced rat paw oedema and showed significant inhibition of oedema. For in vitro COX-inhibitory activity of coumarin derivatives, pyranocoumarin derivative 5a was the most selective (SI = 152) and coumarin-sulfonamide derivative 8d was most active toward COX-2 isozyme. The most active derivatives met the in silico criteria for orally active drugs; thus, they may serve as promising candidates to develop more potent and highly efficient antioxidant, antimicrobial, and\/or anti-inflammatory agents.<\/jats:p>","DOI":"10.3390\/molecules25143251","type":"journal-article","created":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T07:31:28Z","timestamp":1595403088000},"page":"3251","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":121,"title":["Synthesis and Evaluation of New Coumarin Derivatives as Antioxidant, Antimicrobial, and Anti-Inflammatory Agents"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0150-8434","authenticated-orcid":false,"given":"Hanan M.","family":"Alshibl","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebtehal S.","family":"Al-Abdullah","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mogedda E.","family":"Haiba","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"},{"name":"Department of Medicinal Chemistry, National Research Centre, Cairo 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6983-8587","authenticated-orcid":false,"given":"Hamad M.","family":"Alkahtani","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghada E.A.","family":"Awad","sequence":"additional","affiliation":[{"name":"Chemistry of Natural and Microbial Product Department, National Research Centre, Cairo 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahlam H.","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Department of Therapeutic Chemistry, Pharmaceutical and Drug Industries Research Division, National Research Centre, Dokki, Cairo 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4668-9811","authenticated-orcid":false,"given":"Bassant M.M.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Pharmacology Department, Medical Research Division, National Research Centre, Cairo 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9447-2361","authenticated-orcid":false,"given":"Ahmed","family":"Bari","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Villinger","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Chemie, Abteilung Anorganische Chemie, Universit\u00e4t Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"757","DOI":"10.2147\/CIA.S158513","article-title":"Oxidative Stress, Aging, and Diseases","volume":"13","author":"Liguori","year":"2018","journal-title":"Clin. Interv. Aging"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7204","DOI":"10.18632\/oncotarget.23208","article-title":"Inflammatory Responses and Inflammation-Associated Diseases in Organs","volume":"9","author":"Chen","year":"2017","journal-title":"Oncotarget"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s40168-016-0199-5","article-title":"The Structure and Diversity of Human, Animal and Environmental Resistomes","volume":"4","author":"Pal","year":"2016","journal-title":"Microbiome"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/S1473-3099(13)70318-9","article-title":"Antibiotic Resistance\u2014the Need for Global Solutions","volume":"13","author":"Laxminarayan","year":"2013","journal-title":"Lancet Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"124","DOI":"10.2174\/1568026618666180329115523","article-title":"Coumarin Compounds in Medicinal Chemistry: Some Important Examples from the Last Years","volume":"18","author":"Pereira","year":"2018","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1517\/13543776.2012.678835","article-title":"Coumarin-Based Drugs: A Patent Review (2008\u2013Present)","volume":"22","author":"Kontogiorgis","year":"2012","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.saa.2015.03.026","article-title":"Multispectral Studies of DNA Binding, Antioxidant and Cytotoxic Activities of a New Pyranochromene Derivative","volume":"145","author":"Dehkordi","year":"2015","journal-title":"Spectrochim. Acta. A. Mol. Biomol. Spectrosc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.foodchem.2009.11.040","article-title":"Substituted Imino and Amino Derivatives of 4-Hydroxycoumarins as Novel Antioxidant, Antibacterial and Antifungal Agents: Synthesis and in Vitro Assessments","volume":"120","author":"Vukovic","year":"2010","journal-title":"Food Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.apsb.2014.07.001","article-title":"Novel Coumarin\u2013Benzimidazole Derivatives as Antioxidants and Safer Anti-Inflammatory Agents","volume":"4","author":"Arora","year":"2014","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/S0223-5234(99)00119-1","article-title":"Synthesis and Anti-Inflammatory Activity of N-Substituted 2-Oxo-2H-1-Benzopyran-3-Carboxamides and Their 2-Iminoanalogues","volume":"34","author":"Bylov","year":"1999","journal-title":"Eur. J. Med. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4480","DOI":"10.1016\/j.bmcl.2011.06.002","article-title":"Synthesis and Anti-Inflammatory Activity of Novel Biscoumarin\u2013Chalcone Hybrids","volume":"21","author":"Sashidhara","year":"2011","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/S0014-827X(00)00097-5","article-title":"4-Hydroxycoumarin in Heterocyclic Synthesis: Part III. Synthesis of Some New Pyrano[2,3-d]Pyrimidine, 2-Substituted[1,2,4]Triazolo[1,5-c]Pyrimidine and Pyrimido[1,6-b][1,2,4]Triazine Derivatives","volume":"55","author":"Bedair","year":"2000","journal-title":"Il Farm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8965","DOI":"10.1007\/s11164-015-1941-5","article-title":"Synthesis, Photoluminescent, Antibacterial Activities and Theoretical Studies of Three Novel Coumarin and Dihydropyran Derivatives Containing a Triphenylamine Group","volume":"41","author":"Shi","year":"2015","journal-title":"Res. Chem. Intermed."},{"key":"ref_14","first-page":"229","article-title":"Synthesis and Anti-HIV Activity of New Fused Chromene Derivatives Derived from 2-Amino-4-(1-Naphthyl)-5-Oxo-4H,5H-Pyrano[3,2- c]Chromene-3-Carbonitrile","volume":"68","author":"Mohammed","year":"2014","journal-title":"Z. F\u00fcr Naturforschung B"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.jtusci.2014.08.001","article-title":"Synthesis, Spectral Characterization of Some New 3-Heteroaryl Azo 4-Hydroxy Coumarin Derivatives and Their Antimicrobial Evaluation","volume":"9","author":"Sahoo","year":"2015","journal-title":"J. Taibah Univ. Sci."},{"key":"ref_16","first-page":"1","article-title":"Coumarin: A Promising Scaffold for Design and Development of Bioactive Agents","volume":"15","author":"Alshibl","year":"2019","journal-title":"Curr. Bioact. Compd."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1001\/jama.284.10.1247","article-title":"Gastrointestinal Toxicity With Celecoxib vs. Nonsteroidal Anti-Inflammatory Drugs for Osteoarthritis and Rheumatoid Arthritis The CLASS Study: A Randomized Controlled Trial","volume":"284","author":"Silverstein","year":"2000","journal-title":"JAMA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"377","DOI":"10.7326\/0003-4819-101-3-377","article-title":"Sulfasalazine. Pharmacology, Clinical Use, Toxicity, and Related New Drug Development","volume":"101","author":"Peppercorn","year":"1984","journal-title":"Ann. Intern. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1001\/jama.1988.03720080019021","article-title":"Safety and Efficacy of Sulfamethoxazole and Trimethoprim Chemoprophylaxis for Pneumocystis Carinii Pneumonia in AIDS","volume":"259","author":"Fischi","year":"1988","journal-title":"JAMA"},{"key":"ref_20","first-page":"45","article-title":"Pharmacology and Clinical Use of Silver Sulfadiazine and Related Topical Antimicrobial Agents","volume":"8","author":"Fox","year":"1977","journal-title":"Pahlavi Med. J."},{"key":"ref_21","unstructured":"Alshibl, H.M., Al-Abdullah, E.S., and Haiba, M.E. (2019). Coumarin Derivatives. (Application Pending no. 16\/399,950), U.S. Patent."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7847","DOI":"10.1007\/s11164-014-1863-7","article-title":"Efficient Tandem Synthesis of a Variety of Pyran-Annulated Heterocycles, 3,4-Disubstituted Isoxazol-5(4H)-Ones, and \u03b1,\u03b2-Unsaturated Nitriles Catalyzed by Potassium Hydrogen Phthalate in Water","volume":"41","author":"Kiyani","year":"2015","journal-title":"Res. Chem. Intermed."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4093","DOI":"10.1016\/j.bmcl.2004.05.016","article-title":"Synthesis of New Coumarin 3-(N-Aryl) Sulfonamides and Their Anticancer Activity","volume":"14","author":"Reddy","year":"2004","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.13005\/ojc\/300433","article-title":"Antibacterial Activity of Coumarine Derivatives Synthesized from 4-Chloro-Chromen-2-One. The Comparison with Standard Drug","volume":"30","author":"Behrami","year":"2014","journal-title":"Orient. J. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1021\/jf010964p","article-title":"Free Radical Scavenging Properties of Wheat Extracts","volume":"50","author":"Yu","year":"2002","journal-title":"J. Agric. Food Chem."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Qazi, S.S., Li, D., Briens, C., Berruti, F., and Abou-Zaid, M.M. (2017). Antioxidant Activity of the Lignins Derived from Fluidized-Bed Fast Pyrolysis. Mol. Basel Switz., 22.","DOI":"10.3390\/molecules22030372"},{"key":"ref_27","first-page":"113","article-title":"An Antibiotic Assay by Agar-Well Diffusion Method","volume":"15","author":"Pauli","year":"1990","journal-title":"Acta Biologiae et Med. Experimentalis."},{"key":"ref_28","first-page":"161","article-title":"Laboratory Control of Antimicrobial Therapy","volume":"Volume 2","author":"Collee","year":"1989","journal-title":"Practical Medical Microbiology"},{"key":"ref_29","first-page":"3","article-title":"Lipophilicity-Methods of Determination and Its Role in Medicinal Chemistry","volume":"70","author":"Rutkowska","year":"2013","journal-title":"Acta Pol. Pharm."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kalinowska, M., Bajko, E., Matejczyk, M., Kaczy\u0144ski, P., \u0141ozowicka, B., and Lewandowski, W. (2018). The Study of Anti-\/Pro-Oxidant, Lipophilic, Microbial and Spectroscopic Properties of New Alkali Metal Salts of 5-O-Caffeoylquinic Acid. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19020463"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/1521-4184(200102)334:2<35::AID-ARDP35>3.0.CO;2-4","article-title":"Synthesis of Mannich Bases of Some 2,5-Disubstituted 4-Thiazolidinones and Evaluation of Their Antimicrobial Activities","volume":"334","author":"Kocabalkanli","year":"2001","journal-title":"Arch. Pharm. (Weinheim)"},{"key":"ref_32","first-page":"117","article-title":"Synthesis, biological evaluation and molecular modeling studies of some 5-methylisoxazole derivatives as anti-Inflammatory agents","volume":"9","author":"Mohamed","year":"2017","journal-title":"J. Chem. Pharmaceut. Res."},{"key":"ref_33","first-page":"2044","article-title":"Phytochemical and pharmacological studies on newly-suggested herbal formulations for potential protection against inflammatory conditions","volume":"8","author":"Ibrahim","year":"2016","journal-title":"Int. J. Pharmacogn. Phytochem. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/S1043-4682(05)80007-8","article-title":"Neutrophil Proteinases and Matrix Degradation. The Cell Biology of Pericellular Proteolysis","volume":"6","author":"Owen","year":"1995","journal-title":"Semin. Cell Biol."},{"key":"ref_35","first-page":"189","article-title":"In vitro anti-inflammatory activity of methanol extract of Enicostemma axillare","volume":"3","author":"Leelaprakash","year":"2011","journal-title":"Int. J. Drug Dev. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1080\/09540105.2017.1347148","article-title":"Antioxidant and Anti-Inflammatory Activities of Phenolic Compounds Isolated from Melipona Beecheii Honey","volume":"28","year":"2017","journal-title":"Food Agric. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/S1388-1981(99)00147-X","article-title":"The Cyclooxygenase Isoforms: Structural Insights into the Conversion of Arachidonic Acid to Prostaglandins","volume":"1441","author":"Garavito","year":"1999","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2779","DOI":"10.1016\/S0960-894X(99)00481-3","article-title":"Structural Basis of the Dynamic Mechanism of Ligand Binding to Cyclooxygenase","volume":"9","author":"Llorens","year":"1999","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_39","unstructured":"(2018, February 24). Molinspiration Cheminformatics. Available online: http:\/\/www.molinspiration.com."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(00)00129-0","article-title":"Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Discovery and Development Settings","volume":"46","author":"Lipinski","year":"2001","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1021\/js980402t","article-title":"Rapid Calculation of Polar Molecular Surface Area and Its Application to the Prediction of Transport Phenomena. 2. Prediction of Blood\u2013Brain Barrier Penetration","volume":"88","author":"Clark","year":"1999","journal-title":"J. Pharm. Sci."},{"key":"ref_42","first-page":"1289","article-title":"Novel Synthesis of Benzofurans","volume":"53","author":"Bhatt","year":"1984","journal-title":"Curr. Sci."},{"key":"ref_43","first-page":"1","article-title":"Antioxidant and Anti-Inflammatory Activity of Ocimum Labiatum Extract and Isolated Labdane Diterpenoid","volume":"12","author":"Kapewangolo","year":"2015","journal-title":"J. Inflamm. Lond. Engl."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1186\/s12906-018-2260-3","article-title":"Phenolic profile, anti-inflammatory, antinociceptive, anti-ulcerogenic and hepatoprotective activities of Pimenta racemosa leaves","volume":"18","author":"Moharram","year":"2018","journal-title":"BMC Complement Altern Med."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/14\/3251\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:49:10Z","timestamp":1760176150000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/14\/3251"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,16]]},"references-count":44,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2020,7]]}},"alternative-id":["molecules25143251"],"URL":"https:\/\/doi.org\/10.3390\/molecules25143251","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,16]]}}}