{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T02:57:07Z","timestamp":1792119427000,"version":"4.4.0"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T00:00:00Z","timestamp":1786147200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T00:00:00Z","timestamp":1786147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002352","name":"Ain Shams University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002352","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The development of novel antimicrobial and anticancer agents remains a priority due to rising drug resistance and high systemic toxicity of current treatments. A series of novel pyrazole (\n                    <jats:bold>2\u20136<\/jats:bold>\n                    ), pyrimidine (\n                    <jats:bold>7\u201310<\/jats:bold>\n                    ), and pyridine\/oxazinone (\n                    <jats:bold>11\u201314<\/jats:bold>\n                    ) derivatives were synthesized from a chalcone scaffold (\n                    <jats:bold>1<\/jats:bold>\n                    ). They were evaluated for antimicrobial, antibiofilm (\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    ), and cytotoxic (HepG2 cells) activities. Molecular docking and qRT-PCR were performed to study their mechanism. Pyrazoles\n                    <jats:bold>3\u20135<\/jats:bold>\n                    and oxazinone\n                    <jats:bold>13<\/jats:bold>\n                    showed potent antibacterial activity against\n                    <jats:italic>S. aureus<\/jats:italic>\n                    (MIC\u2009=\u20092\u20133.12\u00a0\u00b5g\/mL). Compounds\n                    <jats:bold>4<\/jats:bold>\n                    and\n                    <jats:bold>13<\/jats:bold>\n                    effectively eradicated\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    biofilms, achieving a\u2009\u2265\u20095 log\n                    <jats:sub>10<\/jats:sub>\n                    reduction within 4\u00a0h at 0.8\u2009\u00d7\u2009MIC, driven by disruption of the bacterial respiratory chain. For anticancer activity, compounds\n                    <jats:bold>10<\/jats:bold>\n                    and\n                    <jats:bold>13<\/jats:bold>\n                    selectively reduced HepG2 cell viability to 35\u201340%\n                    <jats:italic>via<\/jats:italic>\n                    oxidative stress-mediated apoptosis. Mechanistically, compound\n                    <jats:bold>4<\/jats:bold>\n                    reduced gyrB expression in\n                    <jats:italic>E. coli<\/jats:italic>\n                    by approximately 4.6-fold, while molecular docking supported its interaction with the ATP-binding pocket of DNA gyrase. Overall, the functionalized heterocycles, particularly compounds\n                    <jats:bold>4<\/jats:bold>\n                    and\n                    <jats:bold>13<\/jats:bold>\n                    , represent promising dual-acting candidates with potent antibacterial, antibiofilm, and selective anticancer activities.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-65144-w","type":"journal-article","created":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T06:44:51Z","timestamp":1786171491000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synthesis and molecular docking of novel pyrazole, pyrimidine, and pyridine derivatives as potent antimicrobial, antibiofilm, and anticancer agents"],"prefix":"10.1038","volume":"16","author":[{"given":"A. M. A.","family":"Hassan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. S.","family":"Essam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selwan","family":"Hamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. H.","family":"Helal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. K.","family":"El-Ziaty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rania S.","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,8]]},"reference":[{"key":"65144_CR1","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1002\/jhet.3435","volume":"56","author":"N Bakthavatchala Reddy","year":"2019","unstructured":"Bakthavatchala Reddy, N. et al. Design and synthesis of some new benzimidazole containing pyrazoles and pyrazolyl thiazoles as potential antimicrobial agents. J. Heterocyclic Chem. 56, 589\u2013596. https:\/\/doi.org\/10.1002\/jhet.3435 (2019).","journal-title":"J. Heterocyclic Chem."},{"key":"65144_CR2","doi-asserted-by":"publisher","first-page":"109","DOI":"10.56431\/p-i63g13","volume":"66","author":"N Desai","year":"2016","unstructured":"Desai, N. & Bhatt, M. J. Optimized synthesis of novel pyrazole based thiazole derivatives and their antimicrobial evaluation. Int. Lett. Chem. Phys. Astron. 66, 109\u2013118 (2016).","journal-title":"Int. Lett. Chem. Phys. Astron."},{"key":"65144_CR3","doi-asserted-by":"publisher","first-page":"343","DOI":"10.4155\/fmc-2021-0275","volume":"14","author":"AM Alam","year":"2022","unstructured":"Alam, A. M. Antibacterial pyrazoles: Tackling resistant bacteria. Future Med. Chem. 14, 343\u2013362. https:\/\/doi.org\/10.4155\/fmc-2021-0275 (2022).","journal-title":"Future Med. Chem."},{"key":"65144_CR4","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.4155\/fmc-2017-0191","volume":"10","author":"M Bhat","year":"2018","unstructured":"Bhat, M. et al. Synthesis and evaluation of thiazolidinone\u2013pyrazole conjugates as anticancer and antimicrobial agents. Future Med. Chem. 10, 1017\u20131036. https:\/\/doi.org\/10.4155\/fmc-2017-0191 (2018).","journal-title":"Future Med. Chem."},{"key":"65144_CR5","doi-asserted-by":"publisher","first-page":"1700223","DOI":"10.1002\/ardp.201700223","volume":"351","author":"MJ Naim","year":"2018","unstructured":"Naim, M. J. et al. Synthesis, docking, in vitro and in vivo antidiabetic activity of pyrazole-based 2, 4-thiazolidinedione derivatives as PPAR-\u03b3 modulators. Arch. Pharm. 351, 1700223. https:\/\/doi.org\/10.1002\/ardp.201700223 (2018).","journal-title":"Arch. Pharm."},{"key":"65144_CR6","doi-asserted-by":"publisher","first-page":"670181","DOI":"10.1155\/2015\/670181","volume":"2015","author":"PA Datar","year":"2015","unstructured":"Datar, P. A. & Jadhav, S. R. Design and synthesis of Pyrazole-3-one derivatives as Hypoglycaemic agents. Int. J. Med. Chem. 2015, 670181. https:\/\/doi.org\/10.1155\/2015\/670181 (2015).","journal-title":"Int. J. Med. Chem."},{"key":"65144_CR7","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1080\/14756366.2016.1180594","volume":"31","author":"HM Faidallah","year":"2016","unstructured":"Faidallah, H. M., Al-Mohammadi, M. M., Alamry, K. A. & Khan, K. A. Synthesis and biological evaluation of fluoropyrazolesulfonylurea and thiourea derivatives as possible antidiabetic agents. J. Enzyme Inhib. Med. Chem. 31, 157\u2013163. https:\/\/doi.org\/10.1080\/14756366.2016.1180594 (2016).","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"65144_CR8","doi-asserted-by":"publisher","first-page":"2054","DOI":"10.21577\/0103-5053.20170050","volume":"28","author":"AAO Abeed","year":"2017","unstructured":"Abeed, A. A. O., Youssef, M. S. K. & Hegazy, R. Synthesis, anti-diabetic and renoprotective activity of some new benzazole, thiazolidin-4-one and azetidin-2-one derivatives. J. Brazilian Chem. Soc. 28, 2054\u20132063. https:\/\/doi.org\/10.21577\/0103-5053.20170050 (2017).","journal-title":"J. Brazilian Chem. Soc."},{"key":"65144_CR9","doi-asserted-by":"publisher","first-page":"1798","DOI":"10.3390\/molecules23071798","volume":"23","author":"Z Yang","year":"2018","unstructured":"Yang, Z., Li, P. & Gan, X. Novel pyrazole-hydrazone derivatives containing an isoxazole moiety: Design, synthesis, and antiviral activity. Molecules 23, 1798. https:\/\/doi.org\/10.3390\/molecules23071798 (2018).","journal-title":"Molecules"},{"key":"65144_CR10","first-page":"126","volume":"9","author":"MS Mohamed","year":"2018","unstructured":"Mohamed, M. S., Zohny, Y. M., El-Senousy, W. M. & Abou El-Elaa, A. M. Synthesis and biological screening of novel pyrazoles and their precursors as potential antiviral agents. Pharmacophore 9, 126\u2013139 (2018).","journal-title":"Pharmacophore"},{"key":"65144_CR11","doi-asserted-by":"publisher","first-page":"1709","DOI":"10.1002\/jhet.3208","volume":"55","author":"IF Nassar","year":"2018","unstructured":"Nassar, I. F., El Farargy, A. F. & Abdelrazek, F. M. Synthesis and anticancer activity of some new fused pyrazoles and their glycoside derivatives. J. Heterocycl. Chem. 55, 1709\u20131719. https:\/\/doi.org\/10.1002\/jhet.3208 (2018).","journal-title":"J. Heterocycl. Chem."},{"key":"65144_CR12","doi-asserted-by":"publisher","first-page":"1955","DOI":"10.1021\/acsomega.7b01784","volume":"3","author":"N Hura","year":"2018","unstructured":"Hura, N., Naaz, A., Prassanawar, S. S., Guchhait, S. K. & Panda, D. Drug-clinical agent molecular hybrid: Synthesis of diaryl (trifluoromethyl) pyrazoles as tubulin targeting anticancer agents. ACS Omega 3, 1955\u20131969. https:\/\/doi.org\/10.1021\/acsomega.7b01784 (2018).","journal-title":"ACS Omega"},{"key":"65144_CR13","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.3389\/fphys.2018.01073","volume":"9","author":"NR Trindade","year":"2018","unstructured":"Trindade, N. R. et al. The newly synthesized pyrazole derivative 5-(1-(3 fluorophenyl)-1 H-pyrazol-4-yl)-2 H-tetrazole reduces blood pressure of spontaneously hypertensive rats via NO\/cGMO pathway. Front. Physiol. 9, 1073. https:\/\/doi.org\/10.3389\/fphys.2018.01073 (2018).","journal-title":"Front. Physiol."},{"key":"65144_CR14","doi-asserted-by":"publisher","first-page":"2","DOI":"10.4103\/0975-7406.171694","volume":"8","author":"MJ Naim","year":"2016","unstructured":"Naim, M. J., Alam, O., Nawaz, F., Alam, M. J. & Alam, P. Current status of pyrazole and its biological activities. J. Pharm. Bioallied Sci. 8, 2. https:\/\/doi.org\/10.4103\/0975-7406.171694 (2016).","journal-title":"J. Pharm. Bioallied Sci."},{"key":"65144_CR15","first-page":"1473","volume":"5","author":"KA Kumar","year":"2013","unstructured":"Kumar, K. A. & Jayaroopa, P. Pyrazoles: Synthetic strategies and their pharmaceutical applications-an overview. Int. J. Pharm. Tech. Res. 5, 1473\u20131486 (2013).","journal-title":"Int. J. Pharm. Tech. Res."},{"key":"65144_CR16","first-page":"1433","volume":"6","author":"MJ Alam","year":"2015","unstructured":"Alam, M. J., Alam, O., Alam, P. & Naim, M. J. A review on pyrazole chemical entity and biological activity. Int. J. Pharm. Sci. Res. 6, 1433\u20131442 (2015).","journal-title":"Int. J. Pharm. Sci. Res."},{"key":"65144_CR17","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1002\/chir.23027","volume":"31","author":"US Goksen","year":"2019","unstructured":"Goksen, U. S. et al. Absolute configuration and biological profile of pyrazoline enantiomers as MAO inhibitory activity. Chirality 31, 21\u201333. https:\/\/doi.org\/10.1002\/chir.23027 (2019).","journal-title":"Chirality"},{"key":"65144_CR18","doi-asserted-by":"publisher","first-page":"279","DOI":"10.3390\/molecules24020279","volume":"24","author":"Y-J Cui","year":"2019","unstructured":"Cui, Y.-J., Tang, L.-Q., Zhang, C.-M. & Liu, Z.-P. Synthesis of novel pyrazole derivatives and their tumor cell growth inhibitory activity. Molecules 24, 279. https:\/\/doi.org\/10.3390\/molecules24020279 (2019).","journal-title":"Molecules"},{"key":"65144_CR19","first-page":"733","volume":"53","author":"C Zalaru","year":"2014","unstructured":"Zalaru, C. et al. Synthesis and biological screening of some novel 2-(1H-pyrazol-1-yl)-acetamides as lidocaine analogue. Ind. J. Chem. B 53, 733\u2013739 (2014).","journal-title":"Ind. J. Chem. B"},{"key":"65144_CR20","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.molstruc.2017.11.073","volume":"1156","author":"C Zalaru","year":"2018","unstructured":"Zalaru, C. et al. Synthesis, spectroscopic characterization, DFT study and antimicrobial activity of novel alkylaminopyrazole derivatives. J. Mol. Struct. 1156, 12\u201321. https:\/\/doi.org\/10.1016\/j.molstruc.2017.11.073 (2018).","journal-title":"J. Mol. Struct."},{"key":"65144_CR21","doi-asserted-by":"publisher","first-page":"134","DOI":"10.3390\/molecules23010134","volume":"23","author":"K Karrouchi","year":"2018","unstructured":"Karrouchi, K. et al. Synthesis and pharmacological activities of pyrazole derivatives: A review. Molecules 23, 134. https:\/\/doi.org\/10.3390\/molecules23010134 (2018).","journal-title":"Molecules"},{"key":"65144_CR22","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.bmc.2017.09.035","volume":"41","author":"M Mamaghani","year":"2021","unstructured":"Mamaghani, M. & Hossein Nia, R. A review on the recent multicomponent synthesis of pyranopyrazoles. Polycyclic Aromat. Compd. 41, 223\u2013291. https:\/\/doi.org\/10.1016\/j.bmc.2017.09.035 (2021).","journal-title":"Polycyclic Aromat. Compd."},{"key":"65144_CR23","doi-asserted-by":"publisher","first-page":"5891","DOI":"10.1016\/j.bmc.2017.09.035","volume":"25","author":"JV Faria","year":"2017","unstructured":"Faria, J. V. et al. Recently reported biological activities of pyrazole compounds. Bioorg. Med. Chem. 25, 5891\u20135903. https:\/\/doi.org\/10.1016\/j.bmc.2017.09.035 (2017).","journal-title":"Bioorg. Med. Chem."},{"key":"65144_CR24","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.bioorg.2018.03.014","volume":"78","author":"MF Harras","year":"2018","unstructured":"Harras, M. F. & Sabour, R. Design, synthesis and biological evaluation of novel 1, 3, 4-trisubstituted pyrazole derivatives as potential chemotherapeutic agents for hepatocellular carcinoma. Bioorg. Chem. 78, 149\u2013157. https:\/\/doi.org\/10.1016\/j.bioorg.2018.03.014 (2018).","journal-title":"Bioorg. Chem."},{"key":"65144_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-323-91221-1.00005-1","author":"TR Allaka","year":"2023","unstructured":"Allaka, T. R. & Katari, N. K. Synthesis of pyridine derivatives for diverse biological activity profiles: a review. Recent Develop. Synthesis Appl. Pyridines https:\/\/doi.org\/10.1016\/B978-0-323-91221-1.00005-1 (2023).","journal-title":"Recent Develop. Synthesis Appl. Pyridines"},{"key":"65144_CR26","doi-asserted-by":"publisher","first-page":"100210","DOI":"10.1016\/j.ejmcr.2024.100210","volume":"12","author":"D Sahu","year":"2024","unstructured":"Sahu, D. et al. Advances in synthesis, medicinal properties and biomedical applications of pyridine derivatives: A comprehensive review. Eur. J. Med. Chem. Rep. 12, 100210. https:\/\/doi.org\/10.1016\/j.ejmcr.2024.100210 (2024).","journal-title":"Eur. J. Med. Chem. Rep."},{"key":"65144_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-026-51574-z","author":"G Algaber","year":"2026","unstructured":"Algaber, G., Shyamala, P., Dammag, Z. & Al-Haddad, M. Design, synthesis and biological evaluation of novel chalcone-derived thioxopyridine and pyrazolopyridine compounds as antimicrobial agents. Sci. Rep. https:\/\/doi.org\/10.1038\/s41598-026-51574-z (2026).","journal-title":"Sci. Rep."},{"key":"65144_CR28","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1007\/s00044-024-03188-1","volume":"33","author":"MA Elsayed","year":"2024","unstructured":"Elsayed, M. A., Elsayed, A. M. & Sroor, F. M. Novel biologically active pyridine derivatives: Synthesis, structure characterization, in vitro antimicrobial evaluation and structure-activity relationship. Med. Chem. Res. 33, 476\u2013491. https:\/\/doi.org\/10.1007\/s00044-024-03188-1 (2024).","journal-title":"Med. Chem. Res."},{"key":"65144_CR29","doi-asserted-by":"publisher","first-page":"4079","DOI":"10.3390\/molecules27134079","volume":"27","author":"RG Yousef","year":"2022","unstructured":"Yousef, R. G. et al. Design, synthesis, in silico and in vitro studies of new immunomodulatory anticancer nicotinamide derivatives targeting VEGFR-2. Molecules 27, 4079. https:\/\/doi.org\/10.3390\/molecules27134079 (2022).","journal-title":"Molecules"},{"key":"65144_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-026-45654-3","author":"HS Khalaf","year":"2026","unstructured":"Khalaf, H. S., El-Rashedy, A. A., Abd El-Gwaad, A. A. & Fayed, A. A. Synthesis, antioxidant and antimicrobial activities, molecular docking study of new pyrimidine derivatives. Sci. Rep. https:\/\/doi.org\/10.1038\/s41598-026-45654-3 (2026).","journal-title":"Sci. Rep."},{"key":"65144_CR31","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1186\/s13065-025-01506-1","volume":"19","author":"J Qurban","year":"2025","unstructured":"Qurban, J. et al. Antimicrobial activity, synthesis, and docking study of some novel arylazo-1, 3-thiazolopyrimidine and arylazo-1, 3-thiazolopyridopyrimidine derivatives. BMC Chem. 19, 148. https:\/\/doi.org\/10.1186\/s13065-025-01506-1 (2025).","journal-title":"BMC Chem."},{"key":"65144_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2025.143602","author":"NA Hamdy","year":"2025","unstructured":"Hamdy, N. A., Khalaf, H. S., Mounier, M. M., El-Ashrey, M. K. & Anwar, M. M. Discovery of novel tetralin-thiazole conjugates as VEGFR-2 inhibitors with anticancer potential: an integrated computational and biological study. J. Mol. Struct. https:\/\/doi.org\/10.1016\/j.molstruc.2025.143602 (2025).","journal-title":"J. Mol. Struct."},{"key":"65144_CR33","doi-asserted-by":"publisher","first-page":"136047","DOI":"10.1016\/j.molstruc.2023.136047","volume":"1291","author":"D Adel","year":"2023","unstructured":"Adel, D., El-Adl, K., Nasr, T., Sakr, T. M. & Zaghary, W. Pyrazolo [3, 4-d] pyrimidine derivatives as EGFRT790M and VEGFR-2 dual TK inhibitors: Design, synthesis, molecular docking, ADMET profile and anticancer evaluations. J. Mol. Struct. 1291, 136047. https:\/\/doi.org\/10.1016\/j.molstruc.2023.136047 (2023).","journal-title":"J. Mol. Struct."},{"key":"65144_CR34","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1007\/s11224-022-01931-1","volume":"33","author":"JS Al-Otaibi","year":"2022","unstructured":"Al-Otaibi, J. S. et al. Insights into solvation, chemical reactivity, structural, vibrational and anti-hypertensive properties of a thiazolopyrimidine derivative by DFT and MD simulations. Struct. Chem. 33, 1271\u20131283. https:\/\/doi.org\/10.1007\/s11224-022-01931-1 (2022).","journal-title":"Struct. Chem."},{"key":"65144_CR35","doi-asserted-by":"publisher","first-page":"111567","DOI":"10.1016\/j.biopha.2021.111567","volume":"139","author":"N Irshad","year":"2021","unstructured":"Irshad, N., Khan, A.-U. & Iqbal, M. S. Antihypertensive potential of selected pyrimidine derivatives: explanation of underlying mechanistic pathways. Biomed. Pharmacother. 139, 111567. https:\/\/doi.org\/10.1016\/j.biopha.2021.111567 (2021).","journal-title":"Biomed. Pharmacother."},{"key":"65144_CR36","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1016\/j.ejmech.2014.10.061","volume":"89","author":"D Kumar","year":"2015","unstructured":"Kumar, D., Khan, S. I., Tekwani, B. L., Ponnan, P. & Rawat, D. S. 4-Aminoquinoline-pyrimidine hybrids: Synthesis, antimalarial activity, heme binding and docking studies. Eur. J. Med. Chem. 89, 490\u2013502. https:\/\/doi.org\/10.1016\/j.ejmech.2014.10.061 (2015).","journal-title":"Eur. J. Med. Chem."},{"key":"65144_CR37","doi-asserted-by":"publisher","first-page":"136304","DOI":"10.1016\/j.molstruc.2023.136304","volume":"1294","author":"SN Sriharsha","year":"2023","unstructured":"Sriharsha, S. N. et al. Novel \u03b2-L-1, 3-thiazolidine pyrimidine nucleoside analogues: design, synthesis, molecular docking, and anti-HIV activity. J. Mol. Struct. 1294, 136304. https:\/\/doi.org\/10.1016\/j.molstruc.2023.136304 (2023).","journal-title":"J. Mol. Struct."},{"key":"65144_CR38","doi-asserted-by":"publisher","first-page":"5292","DOI":"10.1016\/j.ejmech.2010.08.049","volume":"45","author":"R Kumar","year":"2010","unstructured":"Kumar, R. et al. Reinvestigation of structure\u2013activity relationship of methoxylated chalcones as antimalarials: Synthesis and evaluation of 2, 4, 5-trimethoxy substituted patterns as lead candidates derived from abundantly available natural \u03b2-asarone. Eur. J. Med. Chem. 45, 5292\u20135301. https:\/\/doi.org\/10.1016\/j.ejmech.2010.08.049 (2010).","journal-title":"Eur. J. Med. Chem."},{"key":"65144_CR39","doi-asserted-by":"publisher","first-page":"139170","DOI":"10.1016\/j.molstruc.2024.139170","volume":"1317","author":"A Hassan","year":"2024","unstructured":"Hassan, A. et al. Synthesis, characterization, and anticancer effect of novel pyrazolopyranopyrimidines. J. Mol. Struct. 1317, 139170. https:\/\/doi.org\/10.1016\/j.molstruc.2024.139170 (2024).","journal-title":"J. Mol. Struct."},{"key":"65144_CR40","doi-asserted-by":"publisher","first-page":"e202401650","DOI":"10.1002\/cbdv.202401650","volume":"21","author":"A Hassan","year":"2024","unstructured":"Hassan, A., Abubshait, S. A., Abdel-Haleem, D. R., El-Naggar, A. M. & Hassaballah, A. I. Eco-sustainable Synthesis and Potential Efficiency of Some Novel N-containing Heterocyclic Derivatives as Insecticidal and Photosensitizing Agents Against Musca domestica L. Chem. Biodivers. 21, e202401650. https:\/\/doi.org\/10.1002\/cbdv.202401650 (2024).","journal-title":"Chem. Biodivers."},{"key":"65144_CR41","doi-asserted-by":"publisher","first-page":"140405","DOI":"10.1016\/j.molstruc.2024.140405","volume":"1322","author":"M Kamal","year":"2025","unstructured":"Kamal, M. Synthesis and insecticidal assessment of nitrogenous heterocycles derived from 2-pyridone derivative against Culex pipiens L. Larvae. J. Mol. Struct. 1322, 140405. https:\/\/doi.org\/10.1016\/j.molstruc.2024.140405 (2025).","journal-title":"J. Mol. Struct."},{"key":"65144_CR42","doi-asserted-by":"publisher","first-page":"1404","DOI":"10.1080\/10406638.2025.2457965","volume":"45","author":"AY Alzahrani","year":"2025","unstructured":"Alzahrani, A. Y., Danial, E. N., El-Ziaty, A., Ali, R. S. & Hassan, A. Synthesis, characterization, antimicrobial activity and molecular docking studies of novel pyrano [2, 3-c] pyrazole derivatives. Polycyclic Aromat. Compd. 45, 1404\u20131428. https:\/\/doi.org\/10.1080\/10406638.2025.2457965 (2025).","journal-title":"Polycyclic Aromat. Compd."},{"key":"65144_CR43","doi-asserted-by":"publisher","DOI":"10.1080\/10406638.2026.2632129","author":"SA Abubshait","year":"2026","unstructured":"Abubshait, S. A., El-Naggar, A. M., Farag, S. M., Salem, H. H. & Hassan, A. Design, synthesis, molecular modeling, and evaluation of larvicidal efficacy of novel dihydropyrano [2, 3-c] pyrazole derivatives against culex pipiens L. larvae (Diptera: Culicidae). Polycyclic Aromat. Compd. https:\/\/doi.org\/10.1080\/10406638.2026.2632129 (2026).","journal-title":"Polycyclic Aromat. Compd."},{"key":"65144_CR44","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2026.152083","author":"H Abdelmegeed","year":"2026","unstructured":"Abdelmegeed, H. et al. Vanillin-grafted chitosan biopolymers via nucleophilic addition\u2013elimination: A promising bioactive biopolymer for enhanced skin wound repair. Int. J. Biol. Macromol. https:\/\/doi.org\/10.1016\/j.ijbiomac.2026.152083 (2026).","journal-title":"Int. J. Biol. Macromol."},{"key":"65144_CR45","unstructured":"Information, N. C. f. B. (National Center for Biotechnology Information Bethesda, MD, USA, 2021)."},{"key":"65144_CR46","doi-asserted-by":"publisher","first-page":"2990","DOI":"10.1007\/s00044-011-9824-9","volume":"21","author":"K Nepali","year":"2012","unstructured":"Nepali, K. et al. Effect of ring A and ring B substitution on the cytotoxic potential of pyrazole tethered chalcones. Med. Chem. Res. 21, 2990\u20132997. https:\/\/doi.org\/10.1007\/s00044-011-9824-9 (2012).","journal-title":"Med. Chem. Res."},{"key":"65144_CR47","unstructured":"PubChem, B. National Library of Medicine (US). National Center for Biotechnology Information (2004)."},{"key":"65144_CR48","doi-asserted-by":"publisher","first-page":"5319","DOI":"10.3390\/ijms24065319","volume":"24","author":"A Burke","year":"2023","unstructured":"Burke, A. et al. Antimicrobial evaluation of new pyrazoles, indazoles and pyrazolines prepared in continuous flow mode. Int. J. Mol. Sci. 24, 5319. https:\/\/doi.org\/10.3390\/ijms24065319 (2023).","journal-title":"Int. J. Mol. Sci."},{"key":"65144_CR49","doi-asserted-by":"publisher","first-page":"19752","DOI":"10.1039\/d4ra01387e","volume":"14","author":"AA Abbas","year":"2024","unstructured":"Abbas, A. A., Farghaly, T. A. & Dawood, K. M. Recent advances on anticancer and antimicrobial activities of directly-fluorinated five-membered heterocycles and their benzo-fused systems. RSC Adv. 14, 19752\u201319779. https:\/\/doi.org\/10.1039\/d4ra01387e (2024).","journal-title":"RSC Adv."},{"key":"65144_CR50","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.01864-19","author":"MP Weinstein","year":"2020","unstructured":"Weinstein, M. P. & Lewis, J. S. The clinical and laboratory standards institute subcommittee on antimicrobial susceptibility testing: background, organization, functions, and processes. J. Clinic. Microbiol. https:\/\/doi.org\/10.1128\/jcm.01864-19 (2020).","journal-title":"J. Clinic. Microbiol."},{"key":"65144_CR51","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.idc.2015.10.014","volume":"30","author":"MT Albataineh","year":"2016","unstructured":"Albataineh, M. T., Sutton, D. A., Fothergill, A. W. & Wiederhold, N. P. Update from the laboratory: Clinical identification and susceptibility testing of fungi and trends in antifungal resistance. Infect. Dis. Clin. N. Am. 30, 13\u201335. https:\/\/doi.org\/10.1016\/j.idc.2015.10.014 (2016).","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"65144_CR52","doi-asserted-by":"publisher","first-page":"178184","DOI":"10.1016\/j.scitotenv.2024.178184","volume":"959","author":"A Lavrikova","year":"2025","unstructured":"Lavrikova, A., Janda, M., Bujd\u00e1kov\u00e1, H. & Hensel, K. Eradication of single-and mixed-species biofilms of P. aeruginosa and S. aureus by pulsed streamer corona discharge cold atmospheric plasma. Sci. Tot. Environ. 959, 178184. https:\/\/doi.org\/10.1016\/j.scitotenv.2024.178184 (2025).","journal-title":"Sci. Tot. Environ."},{"key":"65144_CR53","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s00284-022-03151-6","volume":"80","author":"S Hamed","year":"2023","unstructured":"Hamed, S. & Emara, M. Antibacterial and antivirulence activities of acetate, zinc oxide nanoparticles, and vitamin C against E. coli O157: H7 and P. aeruginosa. Current Microbiol. 80, 57. https:\/\/doi.org\/10.1007\/s00284-022-03151-6 (2023).","journal-title":"Current Microbiol."},{"key":"65144_CR54","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1002\/jcc.21334","volume":"31","author":"O Trott","year":"2010","unstructured":"Trott, O. & Olson, A. J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 31, 455\u2013461. https:\/\/doi.org\/10.1002\/jcc.21334 (2010).","journal-title":"J. Comput. Chem."},{"key":"65144_CR55","first-page":"243","volume-title":"Chemical Biology: Methods and Protocols","author":"S Dallakyan","year":"2014","unstructured":"Dallakyan, S. & Olson, A. J. Small-molecule library screening by docking with PyRx. In Chemical Biology: Methods and Protocols 243\u2013250 (Springer, 2014)."},{"key":"65144_CR56","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/978-1-0716-4550-5_4","volume-title":"Topoisomerases: Methods and Protocols","author":"S Joshi","year":"2025","unstructured":"Joshi, S. & Osheroff, N. DNA supercoiling catalyzed by bacterial gyrase. In Topoisomerases: Methods and Protocols 39\u201350 (Springer, 2025)."},{"key":"65144_CR57","doi-asserted-by":"publisher","first-page":"10145","DOI":"10.1021\/acsomega.0c00865","volume":"5","author":"F Ushiyama","year":"2020","unstructured":"Ushiyama, F. et al. Lead identification of 8-(methylamino)-2-oxo-1, 2-dihydroquinoline derivatives as DNA gyrase inhibitors: Hit-to-lead generation involving thermodynamic evaluation. ACS Omega 5, 10145\u201310159. https:\/\/doi.org\/10.1021\/acsomega.0c00865 (2020).","journal-title":"ACS Omega"},{"key":"65144_CR58","doi-asserted-by":"publisher","first-page":"2828","DOI":"10.1016\/j.bmcl.2010.03.052","volume":"20","author":"SM Ronkin","year":"2010","unstructured":"Ronkin, S. M. et al. Discovery of pyrazolthiazoles as novel and potent inhibitors of bacterial gyrase. Bioorg. Med. Chem. Lett. 20, 2828\u20132831. https:\/\/doi.org\/10.1016\/j.bmcl.2010.03.052 (2010).","journal-title":"Bioorg. Med. Chem. Lett."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-65144-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-65144-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-65144-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T06:56:53Z","timestamp":1786172213000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-65144-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,8]]},"references-count":58,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["65144"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-65144-w","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,8]]},"assertion":[{"value":"24 June 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no financial or personal relationships that could be construed as a potential conflict of interest concerning the research, authorship, and\/or publication of this work. All authors have approved the final version of the manuscript.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"24543"}}