{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T13:22:14Z","timestamp":1788355334027,"version":"build-2803163510"},"reference-count":50,"publisher":"American Chemical Society (ACS)","issue":"46","license":[{"start":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T00:00:00Z","timestamp":1605052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In this article, a series of benzothiazole-bearing N-sulfonamide 2-pyridone derivatives were synthesized via the reaction of benzothiazole sulfonylhydrazide with sodium salts of both (hydroxymethylene) cycloalkanones and unsaturated ketones, as well as ethoxymethylene derivatives. The structures of the resultant compounds were confirmed using IR, 1H NMR, 13C NMR, 1H\u20131H correlation spectroscopy (COSY), 1H\u201313C heteronuclear multiple bond coherence (HMBC), and 1H\u201313C heteronuclear multiple quantum coherence (HSQC) spectral analysis and elemental analysis. The newly synthesized compounds were evaluated in vitro for their antiviral activities against the HSV-1, HAV HM175, HCVcc genotype 4, CBV4, and HAdV7 viruses. Additionally, the compounds were examined for their cytotoxic effect on five normal cell lines. It was observed that five compounds were found to possess viral reduction of 50% or more against CBV4 with significant IC50, CC50, and SI values. In the case of HSV-1 and HAV HM175 viruses, three compounds have shown more than 50% reduction, while in the case of HCVcc genotype 4 and HAdV7 viruses, only two compounds demonstrated more than 50% reduction. Furthermore, the physicochemical properties of the most active compounds were evaluated. The two most potent compounds against HSV-1 virus, 7e and 13a, were evaluated for their inhibitory activity against USP7. Docking studies using Molecular Operating Environment (MOE) were used to identify the interactions between 7e and 13a compounds and the active site of the USP7 enzyme.<\/jats:p>","DOI":"10.1021\/acsomega.0c04424","type":"journal-article","created":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T16:13:00Z","timestamp":1605111180000},"page":"30023-30036","source":"Crossref","is-referenced-by-count":50,"title":["Novel Synthesis and Antiviral Evaluation of New Benzothiazole-Bearing\n                    <i>N<\/i>\n                    -Sulfonamide 2-Pyridone Derivatives as USP7\nEnzyme Inhibitors"],"prefix":"10.1021","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6807-2110","authenticated-orcid":true,"given":"Rasha A.","family":"Azzam","sequence":"first","affiliation":[{"name":"Helwan University , , ,","place":["Cairo, Egypt, 11795"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba A.","family":"Elboshi","sequence":"additional","affiliation":[{"name":"Helwan University , , ,","place":["Cairo, Egypt, 11795"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3268-5975","authenticated-orcid":true,"given":"Galal H.","family":"Elgemeie","sequence":"additional","affiliation":[{"name":"Helwan University , , ,","place":["Cairo, Egypt, 11795"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,11,11]]},"reference":[{"key":"2026090209083870900_cit1","doi-asserted-by":"publisher","first-page":"272","DOI":"10.3390\/md15090272","article-title":"Current\nstatus and future prospects of marine natural products (MNPs) as antimicrobials","volume":"15","author":"Choudhary","year":"2017","journal-title":"Mar. Drugs."},{"key":"2026090209083870900_cit2","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.2174\/138527205774610886","article-title":"New Synthetic\nMethods to 2-Pyridone Rings","volume":"9","author":"Torres","year":"2005","journal-title":"Curr. Org. Chem."},{"key":"2026090209083870900_cit3","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1002\/ardp.201400340","article-title":"Recent Advances\nin the Chemistry\nand Biology of Benzothiazoles","volume":"348","author":"Gill","year":"2015","journal-title":"Arch. Pharm."},{"key":"2026090209083870900_cit4","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1002\/(SICI)1098-1128(199809)18:5&lt;299::AID-MED2&gt;3.0.CO;2-O","article-title":"Camptothecin\nand taxol: Discovery to clinic","volume":"18","author":"Wall","year":"1998","journal-title":"Med. Res. Rev."},{"key":"2026090209083870900_cit5","doi-asserted-by":"publisher","first-page":"6471","DOI":"10.1021\/ja00227a030","article-title":"Synthesis\nof (.+-.)-fredericamycin A","volume":"110","author":"Kelly","year":"1988","journal-title":"J. Am. Chem. Soc."},{"key":"2026090209083870900_cit6","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1128\/AAC.39.4.964","article-title":"In vitro\nevaluation of ABT-719, a novel DNA gyrase inhibitor","volume":"39","author":"Flamm","year":"1995","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026090209083870900_cit7","unstructured":"Roussel, P.; Heim, J.; Schneider, P.; Bartels, C.; Liu, Y.; Dale, G.; Milligan, D.; Evolva, S. A.\n          2-Pyridone Antimicrobial Compositions. US Patent US8,962,8422015."},{"key":"2026090209083870900_cit8","doi-asserted-by":"publisher","first-page":"3389","DOI":"10.2147\/DDDT.S149615","article-title":"Synthesis,\ncharacterization and antimicrobial evaluation of novel 5-benzoyl-N-substituted\namino- and 5-benzoyl-N-sulfonylamino-4-alkylsulfanyl-2-pyridones","volume":"11","author":"Elgemeie","year":"2017","journal-title":"Drug Des. Dev. Ther."},{"key":"2026090209083870900_cit9","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1016\/j.bmcl.2009.12.102","article-title":"Practical\nand efficient synthesis of pyrano [3, 2-c] pyridone, pyrano [4, 3-b]\npyran and their hybrids with nucleoside as potential antiviral and\nantileishmanial agents","volume":"20","author":"Fan","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2026090209083870900_cit10","unstructured":"Fu, J.; Jin, X.; Lee, P.; Lu, P.; Young, J. M.; Novartis, A. G.\n          Tetracyclic Pyridone Compounds\nas antivirals. US Patent US9,845,3252017."},{"key":"2026090209083870900_cit11","doi-asserted-by":"publisher","first-page":"2837","DOI":"10.1016\/j.bmcl.2012.02.073","article-title":"Design and synthesis of 3-(4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridin-2-yl)-1H-quinolin-2-ones\nas VEGFR-2 kinase inhibitors","volume":"22","author":"Han","year":"2012","journal-title":"Bioorg. Med. Chem.\nLett."},{"key":"2026090209083870900_cit12","doi-asserted-by":"publisher","first-page":"6010","DOI":"10.1016\/j.bmcl.2012.05.019","article-title":"Synthesis\nand evaluation of novel 2-pyridone derivatives as inhibitors of phosphodiesterase3\n(PDE3): A target for heart failure and platelet aggregation","volume":"22","author":"Ravinder","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2026090209083870900_cit13","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.ejmech.2015.10.008","article-title":"Structure\nactivity relationships of 4-hydroxy-2-pyridones: A novel class of\nantituberculosis agents","volume":"106","author":"Ng","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"2026090209083870900_cit14","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1021\/jm901237x","article-title":"Design, Synthesis,\nand Antihepatitis B Virus Activities of Novel\n2-Pyridone Derivatives","volume":"53","author":"Lv","year":"2010","journal-title":"J. Med. Chem."},{"key":"2026090209083870900_cit15","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1007\/s13738-012-0155-7","article-title":"Recent advances in synthesis of 2-pyridones: a key\nheterocycle is revisited","volume":"10","author":"Heravi","year":"2013","journal-title":"J. Iran Chem. Soc."},{"key":"2026090209083870900_cit16","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1080\/14756366.2019.1698036","article-title":"Benzothiazole derivatives\nas anticancer agents","volume":"35","author":"Irfan","year":"2020","journal-title":"J. Enzyme Inhib. Med.\nChem."},{"key":"2026090209083870900_cit17","doi-asserted-by":"publisher","first-page":"19013","DOI":"10.1039\/C4RA02649G","article-title":"Design,\nsynthesis and mode of action of some benzothiazole derivatives bearing\nan amide moiety as antibacterial agents","volume":"4","author":"Singh","year":"2014","journal-title":"RSC\nAdv."},{"key":"2026090209083870900_cit18","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1007\/s00044-019-02378-6","article-title":"Sulfa drug\nanalogs: new classes of\nN-sulfonyl aminated azines and their biological and preclinical importance\nin medicinal chemistry (2000\u20132018)","volume":"28","author":"Elgemeie","year":"2019","journal-title":"Med.\nChem. Res."},{"key":"2026090209083870900_cit19","doi-asserted-by":"publisher","first-page":"5131","DOI":"10.1016\/j.bmcl.2013.07.023","article-title":"Novel cycloalkylthiophene\u2013imine\nderivatives bearing benzothiazole scaffold: Synthesis, characterization\nand antiviral activity evaluation","volume":"23","author":"Ke","year":"2013","journal-title":"Bioorg. Med.\nChem. Lett."},{"key":"2026090209083870900_cit20","doi-asserted-by":"publisher","first-page":"1640","DOI":"10.1021\/acsomega.9b03706","article-title":"Efficient\nsynthesis and docking studies\nof novel benzothiazole-based pyrimidinesulfonamide scaffolds as new\nantiviral agents and Hsp90\u03b1 inhibitors","volume":"5","author":"Azzam","year":"2020","journal-title":"ACS Omega."},{"key":"2026090209083870900_cit21","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1021\/jm00308a018","article-title":"Antimalarials. III.\nBenzothiazole amino alcohols","volume":"11","author":"Burger","year":"1968","journal-title":"J. Med. Chem."},{"key":"2026090209083870900_cit22","doi-asserted-by":"publisher","first-page":"4178","DOI":"10.1016\/j.bmcl.2007.05.048","article-title":"Synthesis\nof benzothiazole semicarbazones as novel anticonvulsants\u2500The\nrole of hydrophobic domain","volume":"17","author":"Siddiqui","year":"2007","journal-title":"Bioorg. Med. Chem.\nLett."},{"key":"2026090209083870900_cit23","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1016\/j.ejmech.2012.01.032","article-title":"Synthesis\nof novel 2-mercapto benzothiazole and 1, 2, 3-triazole based bis-heterocycles:\ntheir anti-inflammatory and anti-nociceptive activities","volume":"49","author":"Shafi","year":"2012","journal-title":"Eur. J. Med. Chem."},{"key":"2026090209083870900_cit24","doi-asserted-by":"publisher","first-page":"2871","DOI":"10.1016\/j.bmcl.2008.03.086","article-title":"Antidiabetic activity of N-(6-substituted-1,3-benzothiazol-2-yl)benzenesulfonamides","volume":"18","author":"Moreno-Di\u0301az","year":"2008","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2026090209083870900_cit25","doi-asserted-by":"publisher","first-page":"240","DOI":"10.3109\/14756366.2012.720572","article-title":"Medicinal\nsignificance of benzothiazole scaffold: an insight view","volume":"28","author":"Sharma","year":"2013","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"2026090209083870900_cit26","first-page":"13","article-title":"Synthesis and cyclization of benzothiazole","volume":"3","author":"Gupta","year":"2010","journal-title":"J. Curr. Pharm. Res."},{"key":"2026090209083870900_cit27","doi-asserted-by":"publisher","first-page":"127194","DOI":"10.1016\/j.molstruc.2019.127194","article-title":"Synthesis of novel pyrido[2,1-b]benzothiazole\nand N-substituted 2-pyridylbenzothiazole derivatives showing remarkable\nfluorescence and biological activities","volume":"1201","author":"Azzam","year":"2020","journal-title":"J. Mol.\nStruct."},{"key":"2026090209083870900_cit28","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1002\/jhet.3439","article-title":"Tailored-design\nsynthesis of sulfapyrimidine derivatives","volume":"56","author":"Azzam","year":"2019","journal-title":"J.\nHeterocycl. Chem."},{"key":"2026090209083870900_cit29","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1007\/s00044-018-2264-z","article-title":"Synthesis and antimicrobial\nevaluation of novel N-substituted\n4-ethylsulfanyl-2-pyridones and triazolopyridines","volume":"28","author":"Azzam","year":"2019","journal-title":"Med. Chem. Res."},{"key":"2026090209083870900_cit30","doi-asserted-by":"publisher","first-page":"1820","DOI":"10.1107\/S2056989017015778","article-title":"Crystal structure\nof N-[6-amino-5-(benzo[d]thiazol-2-yl)-3-cyano-4-methylsulfanyl-2-oxo-1,2-dihydropyridin-1-yl]-4-methylbenzenesulfonamide\ndimethylformamide monosolvate","volume":"E73","author":"Azzam","year":"2017","journal-title":"Acta Crystallogr.,\nSect. E: Crystallogr Commun."},{"key":"2026090209083870900_cit31","doi-asserted-by":"publisher","first-page":"10401","DOI":"10.1021\/acsomega.0c00280","article-title":"Design, synthesis, and antimicrobial\nevaluation of a new series of N-sulfonamide 2-pyridones as dual inhibitors\nof DHPS and DHFR enzymes","volume":"5","author":"Azzam","year":"2020","journal-title":"ACS Omega."},{"key":"2026090209083870900_cit32","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1107\/S2056989017008738","article-title":"Crystal\nstructure\nof N\u2032-[2-(benzo[d]thiazol-2-yl)acetyl]-4-methylbenzenesulfonohydrazide","volume":"E73","author":"Azzam","year":"2017","journal-title":"Acta Crystallogr., Sect. E: Crystallogr Commun."},{"key":"2026090209083870900_cit33","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1107\/S2056989016012196","article-title":"Crystal structure\nof 1-amino-2-oxo-2,5,6,7,8,9-hexahydro-1H-cyclohepta[b]pyridine-3-carbonitrile","volume":"E72","author":"Elgemeie","year":"2016","journal-title":"Acta Crystallogr., Sect. E: Crystallogr Commun."},{"key":"2026090209083870900_cit34","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1107\/S1600536802019177","article-title":"N-(3-Cyano-2-oxo-2,5,6,7,8,9-hexahydro-1H-cyclohepta[b]pyridin-1-yl)-4-methylbenzenesulfonamide","volume":"E58","author":"Elgemeie","year":"2002","journal-title":"Acta Crystallogr., Sect. E: Crystallogr Commun."},{"key":"2026090209083870900_cit35","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1107\/S1600536802018731","article-title":"N-[3-Cyano-2-oxo-5,6,7,8-tetrahydroquinoline-1(2H)-yl]-4-\nmethylbenzenesulfonamide","volume":"E58","author":"Elgemeie","year":"2002","journal-title":"Acta Crystallogr.\nE: Rep. Online"},{"key":"2026090209083870900_cit36","doi-asserted-by":"publisher","first-page":"596","DOI":"10.6023\/cjoc201510014","article-title":"Piperidinium acetate-catalyzed the\nsyntesis of 2,3-disubstituted\nchroman-4-one and 2,2-disubstituted benzofuran-3-one derivatives","volume":"36","author":"Wang","year":"2016","journal-title":"Chin. J. Org. Chem."},{"key":"2026090209083870900_cit37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/jhet.4135","article-title":"Ionic liquid\ncatalyzed one-pot multi-component synthesis of fused pyridine derivatives:\nA strategy for green and sustainable chemistry","author":"Chetan","year":"2020","journal-title":"J. Heterocyclic Chem."},{"key":"2026090209083870900_cit38","doi-asserted-by":"publisher","first-page":"2221","DOI":"10.14233\/ajchem.2014.15657","article-title":"A Facile, eco-friendly,\nproton donor-acceptor catalyzed, one-Pot, three-component synthesis\nof tetrahydrobenzo[b]pyrans","volume":"26","author":"Indrasena","year":"2014","journal-title":"Asian J. Chem."},{"key":"2026090209083870900_cit39","doi-asserted-by":"publisher","first-page":"5300","DOI":"10.1021\/acs.jpcb.7b03191","article-title":"Mechanism of the piperidine-catalyzed knoevenagel condensation\nreaction in methanol: The role of iminium and enolate ions","volume":"121","author":"Dalessandro","year":"2017","journal-title":"J. Phys. Chem. B"},{"key":"2026090209083870900_cit40","doi-asserted-by":"publisher","first-page":"5862","DOI":"10.1016\/j.ejmech.2010.07.069","article-title":"Molecular properties prediction, synthesis and antimicrobial activity\nof some newer oxadiazole derivatives","volume":"45","author":"Bakht","year":"2010","journal-title":"Eur. J.\nMed. Chem."},{"key":"2026090209083870900_cit41","unstructured":"http:\/\/www.simulations-plus.com."},{"key":"2026090209083870900_cit42","doi-asserted-by":"publisher","first-page":"1927","DOI":"10.1021\/jm001101a","article-title":"Experimental\nand computational screening models for the prediction of intestinal\ndrug absorption","volume":"44","author":"Stenberg","year":"2001","journal-title":"J. Med. Chem."},{"key":"2026090209083870900_cit43","doi-asserted-by":"publisher","first-page":"2615","DOI":"10.1021\/jm020017n","article-title":"Molecular properties that influence the oral bioavailability\nof drug candidates","volume":"45","author":"Veber","year":"2002","journal-title":"J. Med. Chem."},{"key":"2026090209083870900_cit44","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1093\/emboj\/16.7.1519","article-title":"A novel\nubiquitin-specific protease is dynamically associated with the PML\nnuclear domain and binds to a herpesvirus regulatory protein","volume":"16","author":"Everett","year":"1997","journal-title":"EMBO J."},{"key":"2026090209083870900_cit45","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1107\/S2053230X14002519","article-title":"A 2.2 \u00c5\nresolution structure\nof the USP7 catalytic domain in a new space group elaborates upon\nstructural rearrangements resulting from ubiquitin binding","volume":"70","author":"Molland","year":"2014","journal-title":"Acta Crystallogr., Sect. F: Struct. Biol. Commun."},{"key":"2026090209083870900_cit46","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1002\/(SICI)1099-1573(199906)13:4&lt;323::AID-PTR448&gt;3.0.CO;2-C","article-title":"Mechanism of antiviral\nactivity of\ntriterpenoid saponins","volume":"13","author":"Simo\u0303es","year":"1999","journal-title":"Phytother. Res."},{"key":"2026090209083870900_cit47","first-page":"101","volume-title":"Understanding\nCell Toxicology:\nPrinciples and Practice","author":"Walum","year":"1990"},{"key":"2026090209083870900_cit48","doi-asserted-by":"publisher","first-page":"1557","DOI":"10.1080\/07328319808004686","article-title":"Penetration\nand Antiviral Activity of Coxsackievirus B3 (Cvb3)-Specific Phosphorothioate\nOligodeoxynucleotides (Ps-Odn)","volume":"17","author":"Schmidtke","year":"1998","journal-title":"Nucleosides,\nNucleotides Nucleic Acids"},{"key":"2026090209083870900_cit49","doi-asserted-by":"publisher","first-page":"5365","DOI":"10.1128\/AAC.01256-12","article-title":"Efficient Replication of Genotype\n3a and 4a Hepatitis C Virus Replicons in Human Hepatoma Cells","volume":"56","author":"Saeed","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026090209083870900_cit50","doi-asserted-by":"publisher","first-page":"T35","DOI":"10.1530\/ERC-14-0516","article-title":"Deubiquitinases and the new therapeutic\nopportunities offered to cancer","volume":"22","author":"Pfoh","year":"2015","journal-title":"Endocr. Relat.\nCancer"}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.0c04424","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/5\/46\/30023\/67755763\/acsomega.0c04424.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/5\/46\/30023\/67755763\/acsomega.0c04424.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T13:08:43Z","timestamp":1788354523000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/5\/46\/30023\/584085\/Novel-Synthesis-and-Antiviral-Evaluation-of-New"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,11]]},"references-count":50,"journal-issue":{"issue":"46","published-online":{"date-parts":[[2020,11,11]]},"published-print":{"date-parts":[[2020,11,24]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.0c04424","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,11]]}}}