{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T15:11:15Z","timestamp":1767798675263,"version":"3.49.0"},"reference-count":41,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003336","name":"Bulgarian National Science Fund","doi-asserted-by":"publisher","award":["KP-06-M69\/2"],"award-info":[{"award-number":["KP-06-M69\/2"]}],"id":[{"id":"10.13039\/501100003336","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The ongoing emergence of antiviral drug resistance underscores the critical need for new broad-spectrum antiviral agents. Sulfonamides and their derivatives have emerged as promising candidates for the development of new antiviral therapeutics. In this study, a series of camphor-10-sulfonamide derivatives was synthesized through a feasible and sustainable synthetic approach starting from naturally available precursors and evaluated for antiviral properties. Their activity was examined against three structurally distinct viruses\u2014herpes simplex virus type 1 (HSV-1), human coronavirus (HCoV-OC43), and feline calicivirus (FCV)\u2014representing both DNA and RNA, enveloped and non-enveloped types. The compounds were examined for their effects on viral replication, the stage of viral adsorption to the cell, and extracellular virions. The weakest cytotoxicity and the most pronounced activity of all the tested substances was demonstrated by the tryptophan derivative 7a. A time-dependent inhibition of the stage of adsorption of HCoV-OC43 (\u0394lg = 2.0 at 120 min) and FCV (\u0394lg = 1.75 at 60 min) to susceptible cells was established, as well as virucidal activity on the three types of virions tested, with the most pronounced effect at 120 min\u2014for HSV-1 (\u0394lg = 2.75) and \u0394lg = 2.0 for HCoV-OC43 and FCV. Molecular docking studies performed using Glide (Schr\u00f6dinger) provided insights into the active conformations of the most effective ligands and predicted possible interactions with relevant viral targets, supporting their potential as lead structures for further therapeutic development.<\/jats:p>","DOI":"10.3390\/ijms27020616","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T12:34:21Z","timestamp":1767789261000},"page":"616","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Camphor-10-Sulfonamide Amino Acid Esters: Synthesis, Antiviral Evaluation, and Molecular Docking Insights"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5125-7992","authenticated-orcid":false,"given":"Krasimira","family":"Dikova","sequence":"first","affiliation":[{"name":"Laboratory Organic Synthesis and Stereochemistry, Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"},{"name":"Centre of Competence \u201cSustainable Utilization of Bio-Resources and Waste of Medicinal and Aromatic Plants for Innovative Bioactive Products\u201d (BIORESOURCES BG), 1000 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4772-4471","authenticated-orcid":false,"given":"Neli","family":"Vilhelmova-Ilieva","sequence":"additional","affiliation":[{"name":"The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str. 26, 1113 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5885-7213","authenticated-orcid":false,"given":"Emilio","family":"Mateev","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University\u2014Sofia, 1000 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4101-7036","authenticated-orcid":false,"given":"Zhanina","family":"Petkova","sequence":"additional","affiliation":[{"name":"Laboratory Organic Synthesis and Stereochemistry, Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"},{"name":"Centre of Competence \u201cSustainable Utilization of Bio-Resources and Waste of Medicinal and Aromatic Plants for Innovative Bioactive Products\u201d (BIORESOURCES BG), 1000 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1016\/S0140-6736(12)61728-0","article-title":"Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: A systematic analysis for the Global Burden of Disease Study 2010","volume":"380","author":"Lozano","year":"2012","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.apsb.2012.10.001","article-title":"Milestones in the discovery of antiviral agents: Nucleosides and nucleotides","volume":"2","year":"2012","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Sodano, F., Gazzano, E., Fruttero, R., and Lazzarato, L. (2022). NO in Viral Infections: Role and Development of Antiviral Therapies. Molecules, 27.","DOI":"10.3390\/molecules27072337"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.virusres.2019.02.011","article-title":"Drug repurposing for new, efficient, broad spectrum antivirals","volume":"264","author":"Risco","year":"2019","journal-title":"Virus Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"325","DOI":"10.3109\/14756366.2014.910202","article-title":"An overview of the alpha-, beta-and gamma-carbonic anhydrases from Bacteria: Can bacterial carbonic anhydrases shed new light on evolution of bacteria?","volume":"30","author":"Capasso","year":"2015","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Supuran, C.T. (2017). Carbonic Anhydrase Inhibition and the Management of Hypoxic Tumors. Metabolites, 7.","DOI":"10.3390\/metabo7030048"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"13995","DOI":"10.1002\/slct.202003959","article-title":"Synthesis, Docking and Antihypertensive Activity of Pyridone Derivatives","volume":"5","author":"Masaret","year":"2020","journal-title":"ChemistrySelect"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.bioorg.2018.09.021","article-title":"Rational design and synthesis of new tetralin-sulfonamide derivatives as potent anti-diabetics and DPP-4 inhibitors: 2D & 3D QSAR, in vivo radiolabeling and bio distribution studies","volume":"81","author":"Anwar","year":"2018","journal-title":"Bioorg. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"133672","DOI":"10.1016\/j.molstruc.2022.133672","article-title":"Sulfonamide diuretic azosemide as an efficient carbonic anhydrase inhibitor","volume":"1268","author":"Ferraroni","year":"2022","journal-title":"J. Mol. Struct."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"524","DOI":"10.2146\/ajhp170279","article-title":"Evaluating off-label uses of acetazolamide","volume":"75","author":"Elefritz","year":"2018","journal-title":"Am. J. Health-Sys. Pharm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1021\/acs.jmedchem.7b01086","article-title":"The Magic of Crystal Structure-Based Inhibitor Optimization: Development of a Butyrylcholinesterase Inhibitor with Picomolar Affinity and in Vivo Activity","volume":"61","author":"Brus","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"126677","DOI":"10.1016\/j.bmcl.2019.126677","article-title":"1,3,4-Oxadiazol-2-ylbenzenesulfonamides as privileged structures for the inhibition of monoamine oxidase B","volume":"29","author":"Shetnev","year":"2019","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.bioorg.2018.11.033","article-title":"Synthesis and antiinflammatory activity of sulfonamides and carboxylates incorporating trimellitimides: Dual cyclooxygenase\/carbonic anhydrase inhibitory actions","volume":"84","author":"Angeli","year":"2019","journal-title":"Bioorg. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"113837","DOI":"10.1016\/j.ejmech.2021.113837","article-title":"Sulfonamide derivatives as potential anti-cancer agents and their SARs elucidation","volume":"226","author":"Wan","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Dolensky, J., Hinteregger, C., Leitner, A., Seebacher, W., Saf, R., Belaj, F., M\u00e4ser, P., Kaiser, M., and Weis, R. (2022). Antiprotozoal Activity of Azabicyclo-Nonanes Linked to Tetrazole or Sulfonamide Cores. Molecules, 27.","DOI":"10.3390\/molecules27196217"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"818","DOI":"10.2174\/1385272822666180122153839","article-title":"Sulfonamides as potential bioactive scaffolds","volume":"22","author":"Khan","year":"2018","journal-title":"Curr. Org. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"100077","DOI":"10.1016\/j.medidd.2020.100077","article-title":"AI drug discovery screening for COVID-19 reveals zafirlukast as a repurposing candidate","volume":"9","author":"Delijewski","year":"2021","journal-title":"Med. Drug Discov."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"12126","DOI":"10.1021\/acs.jafc.1c02467","article-title":"Discovery of Novel Chromone Derivatives Containing a Sulfonamide Moiety as Anti-ToCV Agents through the Tomato Chlorosis Virus Coat Protein-Oriented Screening Method","volume":"69","author":"Jiang","year":"2021","journal-title":"J. Agric. Food Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"10951","DOI":"10.1021\/acs.jmedchem.1c00304","article-title":"Aryl Sulfonamide Inhibits Entry and Replication of Diverse Influenza Viruses via the Hemagglutinin Protein","volume":"64","author":"White","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1007\/s00044-017-2077-5","article-title":"Synthesis and antiviral study of 4-(7,7-dimethyl-4-(piperazin-1-yl)-5,6,7,8tetrahydroquinazolin-2-yl) morpholine derivatives","volume":"27","author":"Selvakumar","year":"2018","journal-title":"Med. Chem. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"10","DOI":"10.15407\/bioorganica2021.01.010","article-title":"New 4-iminohydantoin sulfamide derivatives with antiviral and anticancer activity","volume":"16","author":"Kornii","year":"2021","journal-title":"Ukr. Bioorg. Acta."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"127667","DOI":"10.1016\/j.bmcl.2020.127667","article-title":"Discovery of cyclic sulfonamide derivatives as potent inhibitors of SARS-CoV-2","volume":"31","author":"Shin","year":"2021","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.2174\/1385272825666210608115750","article-title":"Study on Camphor Derivatives and Its Applications: A Review","volume":"25","author":"Bendi","year":"2021","journal-title":"Curr. Org. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1007\/s11172-019-2517-0","article-title":"Synthesis of (1S)-(+)-camphor-10-sulfonic acid derivatives and investigations in vitro and in silico of their antiviral activity as the inhibitors of fi lovirus infections","volume":"68","author":"Sokolova","year":"2019","journal-title":"Russ. Chem. Bull."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1007\/s44371-025-00152-9","article-title":"Principles of green chemistry: Building a sustainable future","volume":"2","author":"Kurul","year":"2025","journal-title":"Discov. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5016","DOI":"10.1002\/ejoc.201800504","article-title":"Straightforward and sustainable synthesis of sulfonamides in water under mild conditions","volume":"36","author":"Eid","year":"2018","journal-title":"Eur. J. Org. Chem."},{"key":"ref_27","first-page":"938486","article-title":"Synthesis, characterization, and antibacterial activities of novel sulfonamides derived through condensation of amino group containing drugs, amino acids, and their analogs","volume":"2015","author":"Qadir","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e3331","DOI":"10.1002\/psc.3331","article-title":"Synthesis of Sulfonopeptides","volume":"27","author":"Xu","year":"2021","journal-title":"J. Pept. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"16027","DOI":"10.1039\/C4RA01346H","article-title":"A simple and eco-sustainable method for the sulfonylation of amines under microwave-assisted solvent-free conditions","volume":"4","author":"Lakrout","year":"2014","journal-title":"RSC Adv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e355","DOI":"10.1055\/s-0044-1796646","article-title":"Recent advances in the synthesis of sulfonamide intermediates","volume":"6","author":"Liu","year":"2024","journal-title":"Pharm. Front."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Breitmaier, E. (2006). Terpenes: Flavors, Fragrances, Pharmaca, Pheromones, Wiley-VCH Verlag GmbH & Co. KGaA.","DOI":"10.1002\/9783527609949"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1134\/S1070428016040011","article-title":"Camphor and its derivatives. Unusual transformations and biological activity","volume":"52","author":"Shokova","year":"2016","journal-title":"Russ. J. Org. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/s41586-025-09438-5","article-title":"A nanobody specific to prefusion glycoprotein B neutralizes HSV-1 and HSV-2","volume":"646","author":"Vollmer","year":"2025","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1038\/s41467-022-30658-0","article-title":"Antigenic structure of the human coronavirus OC43 spike reveals exposed and occluded neutralizing epitopes","volume":"13","author":"Wang","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/s41586-018-0852-1","article-title":"Calicivirus VP2 forms a portal-like assembly following receptor engagement","volume":"565","author":"Conley","year":"2019","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"347","DOI":"10.59393\/amb25410309","article-title":"Antiviral Evaluation of Camphor-Based Sulfonamides against Structurally Diverse Viruses","volume":"41","author":"Petkova","year":"2025","journal-title":"Acta Microbiol. Bulg."},{"key":"ref_37","first-page":"493","article-title":"A simple method of estimating fifty percent endpoints","volume":"27","author":"Reed","year":"1938","journal-title":"Am. J. Hyg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/0378-4274(85)90046-3","article-title":"Toxicity determination in vitro by morphological alterations and neutral red absorption","volume":"24","author":"Borenfreund","year":"1985","journal-title":"Toxicol. Lett."},{"key":"ref_39","unstructured":"(2025, January 01). Cytopathic Effect Inhibition Assay. Creative Diagnostics. Available online: https:\/\/antiviral.creative-diagnostics.com\/cc50-ic50-assay.html."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1038\/s41551-025-01411-x","article-title":"Microfluidics combined with electron microscopy for rapid and high-throughput mapping of antibody-viral glycoprotein complexes","volume":"9","author":"Sewall","year":"2025","journal-title":"Nat. Biomed. Eng."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7106","DOI":"10.1021\/acs.jctc.1c00810","article-title":"Efficient exploration of chemical space with docking and deep learning","volume":"17","author":"Yang","year":"2021","journal-title":"J. Chem. Theory Comput."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/616\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T12:34:27Z","timestamp":1767789267000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/616"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,7]]},"references-count":41,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ijms27020616"],"URL":"https:\/\/doi.org\/10.3390\/ijms27020616","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,7]]}}}