{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:46:55Z","timestamp":1791830815698,"version":"4.3.4"},"reference-count":43,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,11,4]],"date-time":"2023-11-04T00:00:00Z","timestamp":1699056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["23-13-00224"],"award-info":[{"award-number":["23-13-00224"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A novel method for synthesizing 1,2,4-triazole- and tetrazole-containing 4H-thiopyrano[2,3-b]quinolines using a new combination of the thio-Michael and aza-Morita\u2013Baylis\u2013Hillman reactions was developed. Target compounds were evaluated for their cytotoxicities and antiviral activities against influenza A\/Puerto Rico\/8\/34 virus in MDCK cells. The compounds showed low toxicity and some exhibited moderate antiviral activity. Molecular docking identified the M2 channel and polymerase basic protein 2 as potential targets. We observed that the antiviral activity of thiopyrano[2,3-b]quinolines is notably affected by both the nature and position of the substituent within the tetrazole ring, as well as the substituent within the benzene moiety of quinoline. These findings contribute to the further search for new antiviral agents against influenza A viruses among derivatives of thiopyrano[2,3-b]quinoline.<\/jats:p>","DOI":"10.3390\/molecules28217427","type":"journal-article","created":{"date-parts":[[2023,11,4]],"date-time":"2023-11-04T15:41:41Z","timestamp":1699112501000},"page":"7427","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Novel 1,2,4-Triazole- and Tetrazole-Containing 4H-Thiopyrano[2,3-b]quinolines: Synthesis Based on the Thio-Michael\/aza-Morita\u2013Baylis\u2013Hillman Tandem Reaction and Investigation of Antiviral Activity"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3904-3433","authenticated-orcid":false,"given":"Andrey V.","family":"Khramchikhin","sequence":"first","affiliation":[{"name":"Department of Chemistry and Technology of Organic Nitrogen Compounds, Saint Petersburg State Institute of Technology (Technical University), 26 Moskovsky Avenue, 190013 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5618-7917","authenticated-orcid":false,"given":"Mariya A.","family":"Skryl\u2019nikova","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Technology of Organic Nitrogen Compounds, Saint Petersburg State Institute of Technology (Technical University), 26 Moskovsky Avenue, 190013 St. Petersburg, Russia"},{"name":"Saint Petersburg Federal Research Center of the Russian Academy of Sciences (SPC RAS), 39, 14th Line, 199178 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0385-922X","authenticated-orcid":false,"given":"Maxim A.","family":"Gureev","sequence":"additional","affiliation":[{"name":"Center of Bio- and Chemoinformatics, I. M. Sechenov First Moscow State Medical University, 8, Trubetskaya Street, Bld. 2, 119991 Moscow, Russia"},{"name":"St. Petersburg School of Physics, Mathematics and Computer Science, HSE University, 16, Soyuza Pechatnikov Str., 190008 St. Petersburg , Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5224-3771","authenticated-orcid":false,"given":"Vladimir V.","family":"Zarubaev","sequence":"additional","affiliation":[{"name":"Saint Petersburg Pasteur Research Institute of Epidemiology and Microbiology, 14 Mira Street, 197101 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3645-8342","authenticated-orcid":false,"given":"Iana L.","family":"Esaulkova","sequence":"additional","affiliation":[{"name":"Saint Petersburg Pasteur Research Institute of Epidemiology and Microbiology, 14 Mira Street, 197101 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9272-7496","authenticated-orcid":false,"given":"Polina A.","family":"Ilyina","sequence":"additional","affiliation":[{"name":"Saint Petersburg Pasteur Research Institute of Epidemiology and Microbiology, 14 Mira Street, 197101 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5066-3772","authenticated-orcid":false,"given":"Oussama Abdelhamid","family":"Mammeri","sequence":"additional","affiliation":[{"name":"Chemical Analysis and Materials Research Center, St. Petersburg State University, 26, Universitetskii Prospect, Petergof, 198504 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2823-0986","authenticated-orcid":false,"given":"Dar\u2019ya V.","family":"Spiridonova","sequence":"additional","affiliation":[{"name":"Research Park, St. Petersburg State University, 26, Universitetskaya Emb. 7\/9, 199034 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5450-3135","authenticated-orcid":false,"given":"Yuri B.","family":"Porozov","sequence":"additional","affiliation":[{"name":"Center of Bio- and Chemoinformatics, I. 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Sechenov First Moscow State Medical University, 8, Trubetskaya Street, Bld. 2, 119991 Moscow, Russia"},{"name":"St. Petersburg School of Physics, Mathematics and Computer Science, HSE University, 16, Soyuza Pechatnikov Str., 190008 St. Petersburg , Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6628-8540","authenticated-orcid":false,"given":"Vladimir A.","family":"Ostrovskii","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Technology of Organic Nitrogen Compounds, Saint Petersburg State Institute of Technology (Technical University), 26 Moskovsky Avenue, 190013 St. Petersburg, Russia"},{"name":"Saint Petersburg Federal Research Center of the Russian Academy of Sciences (SPC RAS), 39, 14th Line, 199178 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1038\/s41586-019-1717-y","article-title":"A New Twenty-First Century Science for Effective Epidemic Response","volume":"575","author":"Bedford","year":"2019","journal-title":"Nature"},{"key":"ref_2","unstructured":"Kiselev, O.I. (2012). Chemo Drugs and Influenza Chemotherapy, Rostok."},{"key":"ref_3","first-page":"182","article-title":"Tetrazoles","volume":"Volume 6","author":"Black","year":"2022","journal-title":"Comprehensive Heterocyclic Chemistry IV"},{"key":"ref_4","first-page":"78","article-title":"1,2,4-Triazoles","volume":"Volume 5","author":"Black","year":"2022","journal-title":"Comprehensive Heterocyclic Chemistry IV"},{"key":"ref_5","first-page":"217","article-title":"Pyridines and Their Benzo Derivatives: Applications","volume":"Volume 7","author":"Black","year":"2022","journal-title":"Comprehensive Heterocyclic Chemistry IV"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1070\/RCR4864","article-title":"Tetrazoles for Biomedicine","volume":"88","author":"Popova","year":"2019","journal-title":"Russ. Chem. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.ejmech.2019.07.043","article-title":"Role of Sulphur-Heterocycles in Medicinal Chemistry: An Update","volume":"180","author":"Pathania","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1016\/j.apsb.2021.11.018","article-title":"Contemporary Medicinal Chemistry Strategies for the Discovery and Optimization of Influenza Inhibitors Targeting VRNP Constituent Proteins","volume":"12","author":"Hou","year":"2022","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1007\/s10593-021-02917-3","article-title":"Recent Advances on Heterocyclic Compounds with Antiviral Properties","volume":"57","author":"De","year":"2021","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1007\/s40265-020-01350-8","article-title":"Baloxavir Marboxil: A Review in Acute Uncomplicated Influenza","volume":"80","author":"Shirley","year":"2020","journal-title":"Drugs"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3086","DOI":"10.1128\/JVI.02077-15","article-title":"The Synthetic Antiviral Drug Arbidol Inhibits Globally Prevalent Pathogenic Viruses","volume":"90","author":"Borisevich","year":"2016","journal-title":"J. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2023\/1618082","article-title":"Molecular Docking Study for Binding Affinity of 2H-Thiopyrano[2,3-b]Quinoline Derivatives against CB1a","volume":"2023","author":"Sharma","year":"2023","journal-title":"Interdiscip. Perspect. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1080\/10426500500366285","article-title":"Microwave Assisted Synthesis of Some Novel Thiopyrano[2,3-b]Quinolines as a New Class of Antimicrobial Agent","volume":"181","author":"Nandeshwarappa","year":"2006","journal-title":"Phosphorus Sulfur Silicon Relat. Elem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"30826","DOI":"10.1039\/C5RA04795A","article-title":"Facile \u201con Water\u201d Domino Reactions for the Expedient Synthesis of 2H-Thiopyrano[2,3-b]Quinolines","volume":"5","author":"Kumar","year":"2015","journal-title":"RSC Adv."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"67","DOI":"10.3851\/IMP1857","article-title":"Evaluation of a System to Screen for Stimulators of Non-Specific DNA Nicking by HIV-1 Integrase: Application to a Library of 50,000 Compounds","volume":"22","author":"Sudol","year":"2011","journal-title":"Antivir. Chem. Chemother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1002\/anie.199622881","article-title":"Combinatorial Synthesis of Small Organic Molecules","volume":"35","author":"Balkenhohl","year":"1996","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_17","unstructured":"Knochel, P., and Molander, G.A. (2014). Comprehensive Organic Synthesis, Elsevier. [2nd ed.]."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Tietze, L.F. (2014). Domino Reactions: Concepts for Efficient Organic Synthesis, Walter de Gruyter GmbH.","DOI":"10.1002\/9783527671304"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1021\/cr950027e","article-title":"Domino Reactions in Organic Synthesis","volume":"96","author":"Tietze","year":"1996","journal-title":"Chem. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1039\/b613741p","article-title":"The Baylis\u2013Hillman Reaction: A Novel Source of Attraction, Opportunities, and Challenges in Synthetic Chemistry","volume":"36","author":"Basavaiah","year":"2007","journal-title":"Chem. Soc. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9453","DOI":"10.1002\/chem.201001293","article-title":"Asymmetric Synthesis of 4-Amino-4H-Chromenes by Organocatalytic Oxa-Michael\/Aza-Baylis-Hillman Tandem Reactions","volume":"16","author":"Marzo","year":"2010","journal-title":"Chem. Eur. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s10593-022-03083-w","article-title":"Synthesis of Isomeric 4-(N-Methyltetrazolylamino)-2-Phenyl-4H-Thiopyrano[2,3-b]Quinoline-3-Carbaldehydes and 4-Hydroxy-2-Phenyl-4H-Thiopyrano[2,3-b]Quinoline-3-Carbaldehyde Based on Tandem Thiol-Michael and (Aza)-Morita\u2013Baylis\u2013Hillman Reactions and an in Vitro Study of the Activity of the Obtained Compounds against Influenza Virus","volume":"58","author":"Khramchikhin","year":"2022","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5214","DOI":"10.1039\/C8OB00929E","article-title":"Recent Advances in the Annulation of Morita\u2013Baylis\u2013Hillman Adducts","volume":"16","author":"Zhong","year":"2018","journal-title":"Org. Biomol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"75923","DOI":"10.1039\/C5RA13611C","article-title":"Intramolecular Morita\u2013Baylis\u2013Hillman and Rauhut\u2013Currier Reactions. A Catalytic and Atom Economic Route for Carbocycles and Heterocycles","volume":"5","year":"2015","journal-title":"RSC Adv."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1007\/s11030-012-9407-9","article-title":"Combinatorial Synthesis of Chemical Building Blocks 1. Azomethines","volume":"16","author":"Ryabukhin","year":"2012","journal-title":"Mol. Divers."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1021\/ja01632a094","article-title":"Mono-Alkylation of Sodium 5-Aminotetrazole in Aqueous Medium","volume":"76","author":"Henry","year":"1954","journal-title":"J. Am. Chem. Soc."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Zhu, J., Wang, Q., and Wang, M.-X. (2014). Multicomponent Reactions in Organic Synthesis, Wiley.","DOI":"10.1002\/9783527678174"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"30","DOI":"10.18097\/pbmc20206601030","article-title":"Computer-Aided Drug Design: From Discovery of Novel Pharmaceutical Agents to Systems Pharmacology","volume":"66","author":"Poroikov","year":"2020","journal-title":"Biomeditsinskaya Khimiya"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1007\/s10593-014-1496-1","article-title":"Prediction of the Biological Activity Spectra of Organic Compounds Using the Pass Online Web Resource","volume":"50","author":"Filimonov","year":"2014","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1093\/bioinformatics\/16.8.747","article-title":"PASS: Prediction of Activity Spectra for Biologically Active Substances","volume":"16","author":"Lagunin","year":"2000","journal-title":"Bioinformatics"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1126\/science.1093155","article-title":"The Structure and Receptor Binding Properties of the 1918 Influenza Hemagglutinin","volume":"303","author":"Gamblin","year":"2004","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e01569-16","DOI":"10.1128\/mBio.01569-16","article-title":"The Antiviral Mechanism of an Influenza A Virus Nucleoprotein-Specific Single-Domain Antibody Fragment","volume":"7","author":"Hanke","year":"2016","journal-title":"mBio"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2646","DOI":"10.1021\/acs.biochem.5b01087","article-title":"Two Distinctive Binding Modes of Endonuclease Inhibitors to the N-Terminal Region of Influenza Virus Polymerase Acidic Subunit","volume":"55","author":"Fudo","year":"2016","journal-title":"Biochemistry"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5481","DOI":"10.1080\/07391102.2020.1871414","article-title":"Can Molecular Dynamics Explain Decreased Pathogenicity in Mutant Camphecene-Resistant Influenza Virus?","volume":"40","author":"Borisevich","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Zhao, L., Che, J., Zhang, Q., Li, Y., Guo, X., Chen, L., Li, H., Cao, R., and Li, X. (2020). Identification of Novel Influenza Polymerase PB2 Inhibitors Using a Cascade Docking Virtual Screening Approach. Molecules, 25.","DOI":"10.3390\/molecules25225291"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1107\/S2053273314026370","article-title":"SHELXT\u2014Integrated Space-Group and Crystal-Structure Determination","volume":"71","author":"Sheldrick","year":"2015","journal-title":"Acta Crystallogr. A Found. Adv."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1107\/S2053229614024218","article-title":"Crystal Structure Refinement with SHELXL","volume":"71","author":"Sheldrick","year":"2015","journal-title":"Acta Crystallogr. C Struct. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1107\/S0021889808042726","article-title":"OLEX2: A Complete Structure Solution, Refinement and Analysis Program","volume":"42","author":"Dolomanov","year":"2009","journal-title":"J. Appl. Crystallogr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s10822-013-9644-8","article-title":"Protein and Ligand Preparation: Parameters, Protocols, and Influence on Virtual Screening Enrichments","volume":"27","author":"Adzhigirey","year":"2013","journal-title":"J. Comput. Aided Mol. Des."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1038\/nature06531","article-title":"Structure and Mechanism of the M2 Proton Channel of Influenza A Virus","volume":"451","author":"Schnell","year":"2008","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1002\/prot.22102","article-title":"Very Fast Prediction and Rationalization of PKa Values for Protein-Ligand Complexes","volume":"73","author":"Bas","year":"2008","journal-title":"Proteins Struct. Funct. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4291","DOI":"10.1021\/acs.jctc.1c00302","article-title":"OPLS4: Improving Force Field Accuracy on Challenging Regimes of Chemical Space","volume":"17","author":"Lu","year":"2021","journal-title":"J. Chem. Theory Comput."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/0471250953.bi0812s18","article-title":"Flexible Ligand Docking with Glide","volume":"18","author":"Repasky","year":"2007","journal-title":"Curr. Protoc. Bioinform."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/21\/7427\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:17:37Z","timestamp":1760131057000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/21\/7427"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,4]]},"references-count":43,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["molecules28217427"],"URL":"https:\/\/doi.org\/10.3390\/molecules28217427","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,4]]}}}