{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T03:02:04Z","timestamp":1788058924098,"version":"build-2784847793"},"reference-count":40,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T00:00:00Z","timestamp":1733097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Researchers Supporting Project","award":["RSPD2024R980"],"award-info":[{"award-number":["RSPD2024R980"]}]},{"name":"King Saud University, Riyadh, Saudi Arabia","award":["RSPD2024R980"],"award-info":[{"award-number":["RSPD2024R980"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: The increasing prevalence of antimicrobial resistant highlights the urgent need for the new therapeutic agents. This study aimed to design and synthesize fused tricyclic benzimidazole\u2013thiazinone derivatives (CS1\u2013CS10) through a convenient method and evaluate their antimicrobial activity against various microorganisms. Methods: A series of fused tricyclic benzimidazole\u2013thiazinone derivatives was rationally designed and synthesized in one pot by the reaction between trans substituted acrylic acids and 1H-benzo[d]imidazole-2-thiol using coupling reagent TBTU (2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate). The structure of these compounds was confirmed through various spectroscopic techniques like IR, 1H and 13C NMR, the DEPT and 2D-HMQC NMR techniques were also performed to confirm the relation of both carbon and proton. Further, the compounds were in vitro evaluated for their effectiveness against the Candida species and a panel of standard bacterial isolates. Results: The synthesized compounds showed moderate antimicrobial activity. Among all of the compounds, CS4 exhibited potent inhibition against Pseudomonas aeruginosa and Escherichia coli at 256 and 512 \u03bcg\/mL concentrations, respectively. Additional research indicated that compound CS4 demonstrated a synergistic effect after combining with the standard antibacterial drug ciprofloxacin. Conclusions: These results suggest that CS4 is the best-synthesized antibacterial agent particularly in combination therapies. These findings highlight its promise for further development as a novel antibacterial agent.<\/jats:p>","DOI":"10.3390\/antibiotics13121155","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T05:43:43Z","timestamp":1733118223000},"page":"1155","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A Convenient One-Pot Synthesis of Novel Benzimidazole\u2013Thiazinone Derivatives and Their Antimicrobial Activity"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8346-9543","authenticated-orcid":false,"given":"Sabahat","family":"Samreen","sequence":"first","affiliation":[{"name":"Medicinal Chemistry Laboratory, Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1574-4796","authenticated-orcid":false,"given":"Asghar","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Chemical and Life Sciences (SCLS), Jamia Hamdard, New Delhi 110062, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saiema","family":"Ahmedi","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2928-0981","authenticated-orcid":false,"given":"Mohammad","family":"Raghib","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry Laboratory, Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9517-7404","authenticated-orcid":false,"given":"Anzarul","family":"Haque","sequence":"additional","affiliation":[{"name":"Central Laboratories Unit, Qatar University, Doha 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6850-6142","authenticated-orcid":false,"given":"Nikhat","family":"Manzoor","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9769-2557","authenticated-orcid":false,"given":"Afzal","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0507-8451","authenticated-orcid":false,"given":"Mohammad","family":"Abid","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2783-7025","authenticated-orcid":false,"given":"Afreen","family":"Inam","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry Laboratory, Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,2]]},"reference":[{"key":"ref_1","unstructured":"(2012). World Health Organization Global Report for Infectious Diseases of Poverty, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1179\/2047773215Y.0000000030","article-title":"Antimicrobial Resistance: A Global Multifaceted Phenomenon","volume":"109","author":"Prestinaci","year":"2015","journal-title":"Pathog. Glob. Health"},{"key":"ref_3","unstructured":"CDC (2019). Antibiotic Resistance Threats in the United States, 2019, U.S. Department of Health and Human Services, CDC."},{"key":"ref_4","unstructured":"CDC (2022). COVID-19: U.S. Impact on Antimicrobial Resistance, Special Report 2022, U.S. Department of Health and Human Services, CDC."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e187410452202280","DOI":"10.2174\/18741045-v16-e2202280","article-title":"A Review on Medicinally Important Heterocyclic Compounds","volume":"16","author":"Qadir","year":"2022","journal-title":"Open Med. Chem. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100606","DOI":"10.1016\/j.rechem.2022.100606","article-title":"A Review on Biological and Medicinal Impact of Heterocyclic Compounds","volume":"4","author":"Kabir","year":"2022","journal-title":"Results Chem."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Lagard\u00e8re, P., Fersing, C., Masurier, N., and Lisowski, V. (2022). Thienopyrimidine: A Promising Scaffold to Access Anti-Infective Agents. Pharmaceuticals, 15.","DOI":"10.3390\/ph15010035"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Petrou, A., Fesatidou, M., and Geronikaki, A. (2021). Thiazole Ring\u2014A Biologically Active Scaffold. Molecules, 26.","DOI":"10.3390\/molecules26113166"},{"key":"ref_9","first-page":"247","article-title":"Morpholine and Thiomorpholine: A Privileged Scaffold Possessing Diverse Bioactivity Profile","volume":"3","author":"Asirvatham","year":"2021","journal-title":"J. Chem. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"49","DOI":"10.2174\/1874104502014010049","article-title":"A Review: Medicinally Important Nitrogen Sulphur Containing Heterocycles","volume":"14","author":"Sharma","year":"2020","journal-title":"Open Med. Chem. J."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Choudhary, S., and Silakari, O. (2018). Chapter 7\u2014Thiazine: A Versatile Heterocyclic Scaffold for Multifactorial Diseases. Key Heterocycle Cores for Designing Multitargeting Molecules, Elsevier Ltd.","DOI":"10.1016\/B978-0-08-102083-8.00007-8"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Badshah, S.L., and Naeem, A. (2016). Bioactive Thiazine and Benzothiazine Derivatives: Green Synthesis Methods and Their Medicinal Importance. Molecules, 21.","DOI":"10.3390\/molecules21081054"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s00044-015-1495-5","article-title":"Development of Drugs Based on Imidazole and Benzimidazole Bioactive Heterocycles: Recent Advances and Future Directions","volume":"25","author":"Gaba","year":"2016","journal-title":"Med. Chem. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Brishty, S.R., Hossain, M.J., Khandaker, M.U., Faruque, M.R.I., Osman, H., and Rahman, S.M.A. (2021). A Comprehensive Account on Recent Progress in Pharmacological Activities of Benzimidazole Derivatives. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.762807"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"100925","DOI":"10.1016\/j.rechem.2023.100925","article-title":"Benzimidazole and Its Derivatives: Recent Advances (2020\u20132022)","volume":"5","author":"Ebenezer","year":"2023","journal-title":"Results Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4512","DOI":"10.1021\/jo400509n","article-title":"Direct Synthesis of Amides from Carboxylic Acids and Amines Using B(OCH2CF3)3","volume":"78","author":"Lanigan","year":"2013","journal-title":"J. Org. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1016\/j.tet.2004.01.020","article-title":"Recent Development of Peptide Coupling Reagents in Organic Synthesis","volume":"60","author":"Han","year":"2004","journal-title":"Tetrahedron"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.jscs.2010.12.006","article-title":"Recent Development in Peptide Coupling Reagents","volume":"16","year":"2012","journal-title":"J. Saudi Chem. Soc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1021\/jm301654b","article-title":"N-Cinnamoylated Chloroquine Analogues as Dual-Stage Antimalarial Leads","volume":"56","author":"Teixeira","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Sturabotti, E., Vetica, F., Toscano, G., Calcaterra, A., Martinelli, A., Migneco, L.M., and Leonelli, F. (2023). N-Acetyl-l-Phenylalanine Racemization During TBTU Amidation: An In-Depth Study for the Synthesis of Anti-Inflammatory 2-(N-Acetyl)-l-Phenylalanylamido-2-Deoxy-d-Glucose (NAPA). Molecules, 28.","DOI":"10.3390\/molecules28020581"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"127036","DOI":"10.1016\/j.molstruc.2019.127036","article-title":"Synthesis, Crystal Structure, Antioxidant Activity and Dft Study of 2-Aryl-2,3-Dihydro-4H-[1,3]Thiazino[3,2-a]Benzimidazol-4-One","volume":"1199","author":"Cruz","year":"2020","journal-title":"J. Mol. Struct."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1021\/op500305s","article-title":"Large-Scale Applications of Amide Coupling Reagents for the Synthesis of Pharmaceuticals","volume":"20","author":"Dunetz","year":"2016","journal-title":"Org. Process Res. Dev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4321","DOI":"10.1021\/jm701623q","article-title":"From Phenothiazine to 3-Phenyl-1,4-benzothiazine Derivatives as Inhibitors of the Staphylococcus aureus NorA Multidrug Efflux Pump","volume":"51","author":"Sabatini","year":"2008","journal-title":"J. Med. Chem."},{"key":"ref_24","first-page":"146","article-title":"Microwave-Assisted Synthesis of Fluoro, Chloro 2-Substituted Benzimidazole Thiazine Derivatives for Antibacterial and Analgesic Activities","volume":"2","author":"Gayathri","year":"2012","journal-title":"Int. J. Res. Pharm. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Owolabi, B.J., Iraoya, D.I., and Adepoju, T.S. (2019). Synthesis, Characterization and Biological Activities of 2,5-Dimethyl-4-Methoxy[5,6-b]Benzo[2,3-a]Pyrolo-4-Keto Thiazine-1,1-Dioxide. Sci. Res. J. (SCIRJ), 7.","DOI":"10.31364\/SCIRJ\/v7.i12.2019.P1219734"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0968-0896(97)10016-5","article-title":"Azole Derivatives of 1,4-Benzothiazine as Antifungal Agents","volume":"6","author":"Fringuelli","year":"1998","journal-title":"Bioorg. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Karaburun, A.\u00c7., Kaya \u00c7avu\u015fo\u011flu, B., Acar \u00c7evik, U., Osmaniye, D., Sa\u011fl\u0131k, B.N., Levent, S., \u00d6zkay, Y., Koparal, A.S., and Kaplanc\u0131kl\u0131, Z.A. (2019). Synthesis and Antifungal Potential of Some Novel Benzimidazole-1,3,4-Oxadiazole Compounds. Molecules, 24.","DOI":"10.3390\/molecules24010191"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"30469","DOI":"10.1039\/D4RA03520H","article-title":"Synthesis and Elucidation of Strained Galactopyronose Esters As Selective Cyclooxygenase-2 Inhibitor: A Comprehensive Computational Approach","volume":"14","author":"Musa","year":"2024","journal-title":"RSC Adv."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4066","DOI":"10.1021\/acs.jmedchem.5b00104","article-title":"PkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures","volume":"58","author":"Pires","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"113224","DOI":"10.1016\/j.ejmech.2021.113224","article-title":"Discovery of New Phenyl Sulfonyl-Pyrimidine Carboxylate Derivatives As the Potential Multi-Target Drugs with Effective Anti-Alzheimer\u2019s Action: Design, Synthesis, Crystal Structure and In-Vitro Biological Evaluation","volume":"215","author":"Manzoor","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_31","unstructured":"Rex, J.H., Alexander, B.D., Andes, D., Arthington-Skaggs, B., Brown, S.D., Chaturvedi, V., Ghannoum, M.A., Espinel-Ingroff, A., Knapp, C.C., and Ostrosky-Zeichner, L. (2008). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts, Clinical and Laboratory Standards Institute. [3rd ed.]. Approved Standard."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.mycmed.2016.04.004","article-title":"Anti-Candida Activity of Geraniol Involves Disruption of Cell Membrane Integrity and Function","volume":"26","author":"Sharma","year":"2016","journal-title":"J. Mycol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"100285","DOI":"10.1016\/j.phyplu.2022.100285","article-title":"Limonene Inhibits Virulence Associated Traits in Candida Albicans: In-Vitro and In-Silico Studies","volume":"2","author":"Ahmedi","year":"2022","journal-title":"Phytomedicine Plus"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Jorgensen, J.H., and Turnidge, J. (2015). Susceptibility Test Methods: Dilution and Disk Diffusion Methods. Manual of Clinical Microbiology, Wiley.","DOI":"10.1128\/9781555817381.ch71"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"27798","DOI":"10.1021\/acsomega.1c03379","article-title":"Development of Oxadiazole-Sulfonamide-Based Compounds as Potential Antibacterial Agents","volume":"6","author":"Ali","year":"2021","journal-title":"ACS Omega"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1089\/fpd.2017.2283","article-title":"National Antimicrobial Resistance Monitoring System: Two Decades of Advancing Public Health Through Integrated Surveillance of Antimicrobial Resistance","volume":"14","author":"Karp","year":"2017","journal-title":"Foodborne Pathog. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Khan, S.A., Asiri, A.M., Basisi, H.M., Asad, M., Zayed, M.E.M., Sharma, K., and Wani, M.Y. (2019). Synthesis and Evaluation of Quinoline-3-Carbonitrile Derivatives as Potential Antibacterial Agents. Bioorg. Chem., 88.","DOI":"10.1016\/j.bioorg.2019.102968"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Abass, S., Zahiruddin, S., Ali, A., Irfan, M., Jan, B., Haq, Q.M.R., Husain, S.A., and Ahmad, S. (2022). Development of Synergy-Based Combination of Methanolic Extract of Andrographis Paniculata and Berberis Aristata Against E. coli and S. aureus. Curr. Microbiol., 79.","DOI":"10.1007\/s00284-022-02911-8"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1128\/AAC.37.3.613","article-title":"Reproducibility of the Microdilution Checkerboard Method for Antibiotic Synergy","volume":"37","author":"Rand","year":"1993","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1128\/AAC.50.3.1096-1099.2006","article-title":"Potent in Vitro Synergism of Fluconazole and Berberine Chloride Against Clinical Isolates of Candida Albicans Resistant to Fluconazole","volume":"50","author":"Quan","year":"2006","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/13\/12\/1155\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:44:37Z","timestamp":1760114677000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/13\/12\/1155"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,2]]},"references-count":40,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["antibiotics13121155"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics13121155","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,2]]}}}