{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T04:22:23Z","timestamp":1782188543157,"version":"3.54.5"},"reference-count":40,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2016,10,9]],"date-time":"2016-10-09T00:00:00Z","timestamp":1475971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"publisher","award":["(RG -257-1435-1436)"],"award-info":[{"award-number":["(RG -257-1435-1436)"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A one-pot reaction was described that results in various pyrazole-thiobarbituric acid derivatives as new pharmacophore agents. These new heterocycles were synthesized in high yields with a broad substrate scope under mild reaction conditions in water mediated by NHEt2. The molecular structures of the synthesized compounds were assigned based on different spectroscopic techniques. The new compounds were evaluated for their antibacterial and antifungal activity. Compounds 4h and 4l were the most active compounds against C. albicans with MIC = 4 \u00b5g\/L. Compound 4c exhibited the best activity against S. aureus and E. faecalis with MIC = 16 \u00b5g\/L. However, compounds 4l and 4o were the most active against B. subtilis with MIC = 16 \u00b5g\/L. Molecular docking studies for the final compounds and standard drugs were performed using the OpenEye program.<\/jats:p>","DOI":"10.3390\/molecules21101337","type":"journal-article","created":{"date-parts":[[2016,10,10]],"date-time":"2016-10-10T10:35:19Z","timestamp":1476095719000},"page":"1337","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Synthesis of Pyrazole-Thiobarbituric Acid Derivatives: Antimicrobial Activity and Docking Studies"],"prefix":"10.3390","volume":"21","author":[{"given":"Yaseen","family":"Elshaier","sequence":"first","affiliation":[{"name":"Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Assuit 71524, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7885-3201","authenticated-orcid":false,"given":"Assem","family":"Barakat","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science, King Saud University, P. O. Box 2455, Riyadh-11451, Saudi Arabia"},{"name":"Department of Chemistry, Faculty of Science, Alexandria University, P. O. Box 426, Ibrahimia, Alexandria 21321, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bander","family":"Al-Qahtany","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science, King Saud University, P. O. Box 2455, Riyadh-11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Al-Majid","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science, King Saud University, P. O. Box 2455, Riyadh-11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9868-0355","authenticated-orcid":false,"given":"Mohamed","family":"Al-Agamy","sequence":"additional","affiliation":[{"name":"Microbiology and Immunology Department, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt"},{"name":"Division of Microbiology, Pharmaceutics Department, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.3390\/molecules13071501","article-title":"Synthesis and antimicrobial activity of some new pyrazole, fused pyrazolo[3,4-d]-pyrimidine and pyrazolo[4,3-e][1,2,4]-triazolo[1,5-c]pyrimidine derivatives","volume":"13","author":"Abunada","year":"2008","journal-title":"Molecules"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.3987\/REV-07-613","article-title":"Pyrazole chemistry in crop protection","volume":"71","author":"Lamberth","year":"2007","journal-title":"Heterocycles"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5161","DOI":"10.1021\/jm051292n","article-title":"Preparation and optimization of a series of 3-carboxamido-5-phenacylaminopyrazole bradykinin B1 receptor antagonists","volume":"50","author":"Dressen","year":"2007","journal-title":"J. Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3223","DOI":"10.1021\/jm0101343","article-title":"Three-dimensional quantitative structure-activity relationships of cyclo-oxygenase-2 (COX-2) inhibitors: A comparative molecular field analysis","volume":"44","author":"Chavatte","year":"2001","journal-title":"J. Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1002\/art.10426","article-title":"The safety of celecoxib in patients with aspirin-sensitive asthma","volume":"46","author":"Woessner","year":"2002","journal-title":"Arthritis Rheum."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1038\/ijo.2009.132","article-title":"Cannabinoid-1 receptor inverse agonists: Current understanding of mechanism of action and unanswered questions","volume":"33","author":"Fong","year":"2009","journal-title":"Int. J. Obes."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.1016\/j.ejmech.2008.01.043","article-title":"Rational design, synthesis and biological evaluation of new 1,5-diarylpyrazole derivatives as CB1 receptor antagonists, structurally related to rimonabant","volume":"43","author":"Menozzi","year":"2008","journal-title":"Eur. J. Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1016\/j.bmcl.2007.11.120","article-title":"Pyrazolopyridines with potent activity against herpesviruses: Effects of C5 substituents on antiviral activity","volume":"18","author":"Gudmundsson","year":"2008","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"11000","DOI":"10.1016\/j.tet.2007.08.052","article-title":"Synthesis of novel Dipyrazolo [3,4-b:3,4-d] pyridines and study of their fluorescence behavior","volume":"63","author":"Kendre","year":"2007","journal-title":"Tetrahedron"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5800","DOI":"10.1016\/j.bmcl.2008.09.057","article-title":"One-pot synthesis and antibacterial activities of pyrazolo [4\u2032,3\u2032:5,6] pyrido [2,3-d] pyrimidine-dione derivatives","volume":"18","author":"Bazgira","year":"2008","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1039\/a808223e","article-title":"Solvent-free organic syntheses. Using supported reagents and microwave irradiation","volume":"1","author":"Varma","year":"1999","journal-title":"Green Chem."},{"key":"ref_12","first-page":"88","article-title":"Reaction of 5-amino-4-formyl-3-methyl (or phenyl)-1-phenyl-1H-pyrazoles with active methylene compounds: Synthesis of fused heterocyclic rings","volume":"36B","author":"Ahluwalia","year":"1997","journal-title":"Indian J. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3003","DOI":"10.1055\/s-0029-1216975","article-title":"Asymmetric syntheses of oxindole and indole spirocyclic alkaloid natural products","volume":"18","author":"Trost","year":"2009","journal-title":"Synthesis"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3821","DOI":"10.1016\/j.ejmech.2009.05.010","article-title":"A facile synthesis and antimycobacterial evaluation of novel spiro-pyrido-pyrrolizines and pyrrolidines","volume":"44","author":"Perumal","year":"2009","journal-title":"Eur. J. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"8949","DOI":"10.1016\/j.tetlet.2004.09.174","article-title":"A new class of metal-free catalysts for direct diastereo-and regioselective Mannich reactions in aqueous media","volume":"45","author":"Wu","year":"2004","journal-title":"Tetrahedron Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.ejmech.2016.02.005","article-title":"Tricyclic pyrazoles. Part 8. Synthesis, biological evaluation and modelling of tricyclic pyrazole carboxamides as potential CB2 receptor ligands with antagonist\/inverse agonist properties","volume":"112","author":"Deiana","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1021\/acsmedchemlett.5b00036","article-title":"Pyrazolo-Piperidines Exhibit Dual Inhibition of CCR5\/CXCR4 HIV Entry and Reverse Transcriptase","volume":"6","author":"Cox","year":"2015","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1007\/s00894-011-1190-5","article-title":"Docking-based 3D-QSAR analyses of pyrazole derivatives as HIV-1 non-nucleoside reverse transcriptase inhibitors","volume":"18","author":"Cichero","year":"2012","journal-title":"J. Mol. Model."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.ejmech.2014.07.026","article-title":"Zwitterionic pyrimidinium adducts as antioxidants with therapeutic potential as nitric oxide scavenger","volume":"84","author":"Barakat","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"o1860","DOI":"10.1107\/S160053680902618X","article-title":"Pyridinium 5-[(1,3-diethyl-6-hydroxy-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl)(2-methoxyphenyl) methyl]-1,3-diethyl-4,6-dioxo-2-thioxopyrimidin-5-ide","volume":"65","author":"Asiri","year":"2009","journal-title":"Acta Crystallogr. Sect. E Struct. Rep. Online"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1007\/s00706-015-1512-x","article-title":"Non-catalytic multicomponent rapid and efficient approach to 10-(2,4,6-trioxohexahydropyrimidin-5-yl)-3,3-dimethyl-2, 3,4,9-tetrahydro-1H-xanthen-1-ones from salicylaldehydes, dimedone, and barbituric acids","volume":"146","author":"Elinson","year":"2015","journal-title":"Mon. Chem. Chem. Mon."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ahluwalia, V.K., Goyal, B., and Das, U. (1997). One-pot Syntheses of 5-Oxo-1,4,5,6,7,8-hexahydroquinolines and Pyrimido [4,5-b] quinolines using Microwave Irradiation and Ultrasound. J. Chem. Res. Synop., 7.","DOI":"10.1039\/a608002b"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1248\/cpb.58.516","article-title":"Chromeno [2,3-d] pyrimidine-triones synthesis by a three-component coupling reaction","volume":"58","author":"Ghahremanzadeh","year":"2010","journal-title":"Chem. Pharm. Bull."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1002\/jhet.5570400310","article-title":"Preparation of 5,5\u2032-pyrilidene and 5,5\u2032-quinolidene bis-barbituric acid derivatives","volume":"40","author":"Jursic","year":"2003","journal-title":"J. Heterocycl. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Barakat, A., Al-Majid, A.M., Al-Ghamdi, A.M., Mabkhot, Y.N., Rafiq Siddiqui, M., Ghabbour, H.A., and Fun, H.K. (2014). Tandem Aldol-Michael reactions in aqueous diethylamine medium: A greener and efficient approach to dimedone-barbituric acid derivatives. Chem. Cent. J., 8.","DOI":"10.1186\/1752-153X-8-9"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4909","DOI":"10.1039\/c3ra46551a","article-title":"An efficient and green procedure for synthesis of rhodanine derivatives by Aldol-Thia-Michael protocol using aqueous diethylamine","volume":"4","author":"Barakat","year":"2014","journal-title":"RSC Adv."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1016\/0006-2952(85)90335-1","article-title":"5-(N-phenylcarboxamido)-2-thiobarbituric acid (NSC 336628), a novel potential antitumor agent","volume":"34","author":"Brewer","year":"1985","journal-title":"Biochem. Pharm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.3390\/molecules19011150","article-title":"A Greener, Efficient Approach to Michael Addition of Barbituric acid to Nitroalkene in Aqueous Diethylamine Medium","volume":"19","author":"Barakat","year":"2014","journal-title":"Molecules"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"23762","DOI":"10.3390\/ijms141223762","article-title":"Tandem Aldol-Michael reactions in aqueous diethylamine medium: A greener and efficient approach to bis-pyrimidine derivatives","volume":"14","author":"Barakat","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4041","DOI":"10.1007\/s11164-015-2257-1","article-title":"Molecular structure investigation and biological evaluation of Michael adducts derived from dimedone","volume":"42","author":"Barakat","year":"2016","journal-title":"Res. Chem. Intermed."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6984","DOI":"10.1016\/j.tetlet.2015.10.108","article-title":"Synthesis of novel 5-monoalkylbarbiturates derivatives-new access to 1,2-oxazepines","volume":"56","author":"Barakat","year":"2015","journal-title":"Tetrahedron Lett."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Barakat, A., Al-Majid, A.M., Lotfy, G., Arshad, F., Yousuf, S., Choudhary, M.I., Ashraf, S., and Ul-Haq, Z. (2015). Synthesis and dynamics studies of barbituric acid derivatives as urease inhibitors. Chem. Cent. J., 9.","DOI":"10.1186\/s13065-015-0140-1"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ejmech.2016.07.072","article-title":"Evaluation of selected 3D virtual screening tools for the prospective identification of peroxisome proliferator-activated receptor (PPAR) \u03b3 partial agonists","volume":"124","author":"Kaserer","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1111\/cbdd.12367","article-title":"Further insights into the pharmacology of the human trace amine-associated receptors: Discovery of novel ligands for TAAR1 by a virtual screening approach","volume":"84","author":"Cichero","year":"2014","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4982","DOI":"10.1128\/AAC.00925-15","article-title":"Structural insights into binding of the antifungal drug fluconazole to Saccharomyces cerevisiae lanosterol 14\u03b1-demethylase","volume":"59","author":"Sagatova","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_36","unstructured":"Available online: http:\/\/www.rcsb.org\/pdb\/explore\/explore.do?structureId=3Q70."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1073\/pnas.1525047113","article-title":"Crystal structure and stability of gyrase-fluoroquinolone cleaved complexes from Mycobacterium tuberculosis","volume":"113","author":"Blower","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1021\/cb5001197","article-title":"Structures of kibdelomycin bound to Staphylococcus aureus GyrB and ParE showed a novel U-shaped binding mode","volume":"19","author":"Lu","year":"2014","journal-title":"ACS Chem. Biol."},{"key":"ref_39","unstructured":"BSAC Methods for Antimicrobial Susceptibility Testing\u2014Version 14. Available online: http:\/\/bsac.org.uk\/wp-content\/uploads\/2012\/02\/BSAC-Susceptibility-testing-version-14.pdf."},{"key":"ref_40","unstructured":"Available online: http:\/\/www.eyesopen.com."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/21\/10\/1337\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:32:35Z","timestamp":1760211155000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/21\/10\/1337"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10,9]]},"references-count":40,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2016,10]]}},"alternative-id":["molecules21101337"],"URL":"https:\/\/doi.org\/10.3390\/molecules21101337","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10,9]]}}}