{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:52:30Z","timestamp":1791183150070,"version":"4.1.0"},"reference-count":89,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Bacterial infections are significant issues that endanger public health and deplete financial resources. A potential strategy to combat these infections is molecular hybridization, which combines pharmacophores from potential drugs to produce hybrid scaffolds that are more effective. The preparation of pyridines attached to pyrazolopyrimidine units with promising antimicrobial potency and dual inhibitory capacity against DNA gyrase and dihydrofolate reductase (DHFR) is the aim of this work. A green procedure was conducted by reacting the suitable 2\u2010cyanoacetamides with aromatic aldehydes and malononitrile in refluxing ethanol for 5\u20138\u2009h containing choline hydroxide to give pyrazolopyrimidine\u2010linked 4\u2010arylpyridine\u20103,5\u2010dicarbonitrile hybrids\n                    <jats:bold>1<\/jats:bold>\n                    and\n                    <jats:bold>2<\/jats:bold>\n                    in 74%\u201394% yields. In general, 5,7\u2010diphenylpyrazolopyrimidine\u2010linked pyridines\n                    <jats:bold>2<\/jats:bold>\n                    showed slightly more increased antibacterial activity, particularly against methicillin\u2010resistant\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    (MRSA), compared to 5,7\u2010dimethylpyrazolopyrimidine\u2010linked pyridines\n                    <jats:bold>1<\/jats:bold>\n                    . The presence of\n                    <jats:italic>para\u2010<\/jats:italic>\n                    substituted arene units at pyridine\u2010C4 connected to electron\u2010withdrawing groups resulted in increased efficacy. Pyridines\n                    <jats:bold>1d<\/jats:bold>\n                    and\n                    <jats:bold>2d<\/jats:bold>\n                    , attached to 4\u2010nitrophenyl groups, showed good potency with MIC\/MBC of 2.52\/5.04 and 2.03\/4.07\u2009\u00b5M against\n                    <jats:italic>S. aureus<\/jats:italic>\n                    and\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    , and with MIC\/MBC of 5.04\/20.17 and 4.07\/16.26\u2009\u00b5M against MRSA.\n                    <jats:bold>1d<\/jats:bold>\n                    and\n                    <jats:bold>2d<\/jats:bold>\n                    showed promising potency with IC\n                    <jats:sub>50<\/jats:sub>\n                    of 3.296 and 3.002\u2009\u03bcM against\n                    <jats:italic>S. aureus<\/jats:italic>\n                    DNA gyrase, IC\n                    <jats:sub>50<\/jats:sub>\n                    of 3.702 and 3.304\u2009\u03bcM against\n                    <jats:italic>E. coli<\/jats:italic>\n                    DNA gyrase, and IC\n                    <jats:sub>50<\/jats:sub>\n                    of 0.171 and 0.162\u2009\u00b5M against\n                    <jats:italic>E. coli<\/jats:italic>\n                    DHFR.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70352","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:26:22Z","timestamp":1791181582000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual DHFR and DNA Gyrase Inhibitory Potency of Some Novel Pyridine Hybrids Linked to Pyrazolo[1,5\u2010\n                    <i>a<\/i>\n                    ]Pyrimidine Units: Antibacterial Screening and SAR Study"],"prefix":"10.1002","volume":"359","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1325-036X","authenticated-orcid":false,"given":"Ahmed A. M.","family":"Ahmed","sequence":"first","affiliation":[{"name":"Department of Chemistry, College of Science Jouf University Sakaka Aljouf Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8226-010X","authenticated-orcid":false,"given":"Ahmed E. M.","family":"Mekky","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science Cairo University Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed H.","family":"Alanazi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science Jouf University Sakaka Aljouf Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7844-9507","authenticated-orcid":false,"given":"Sultan A.","family":"Alsahli","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science Jouf University Sakaka Aljouf Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherif M. H.","family":"Sanad","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science Cairo University Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2025.108350","article-title":"Structure\u2010Based Molecular Hybridization Design and Synthesis of Keap1\u2010Nrf2 Inhibitors for Anti\u2010Inflammatory Treatment","volume":"158","author":"Qin X.","year":"2025","journal-title":"Bioorganic Chemistry"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.molstruc.2026.145308","article-title":"Synthesis and Antibacterial Activity of Some New Pyrazoles Incorporating Benzimidazole or Indole Moiety","volume":"1357","author":"El\u2010Ossaily Y. 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M.","year":"2026","journal-title":"ChemistrySelect"},{"key":"e_1_2_8_8_1","article-title":"Navigating Antimicrobials and Combating Antimicrobial Resistance: Challenges, Impacts, and Strategies for Global Action","volume":"17","author":"Desai V.","year":"2025","journal-title":"Cureus"},{"key":"e_1_2_8_9_1","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.mpmed.2017.07.006","article-title":"Antibiotic Resistance","volume":"45","author":"MacGowan A.","year":"2017","journal-title":"Medicine"},{"key":"e_1_2_8_10_1","doi-asserted-by":"crossref","first-page":"9710","DOI":"10.1002\/slct.201902828","article-title":"Microwave Assisted Three Component One\u2010Pot Synthesis of Bis(Aminoazolo[1,5\u2010A]Pyrimidines) and Bis(Aminoazino[1,2\u2010A]Benzimidazoles) Bearing Thiazole Moiety","volume":"4","author":"Mekky A. E. 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A.","year":"2026","journal-title":"Archiv der Pharmazie"},{"key":"e_1_2_8_14_1","doi-asserted-by":"crossref","first-page":"3539","DOI":"10.3390\/ijms25063539","article-title":"Unveiling the Hidden Regulators: The Impact of lncRNAs on Zoonoses","volume":"25","author":"Xu B.","year":"2024","journal-title":"International Journal of Molecular Sciences"},{"key":"e_1_2_8_15_1","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1080\/00397911.2026.2675325","article-title":"New Chromene\u2010Based 1\u2010Aryl\u20101H\u2010Pyrazole\u20103\u2010Carboxylate Hybrids Linked to 1,3,4\u2010Oxadiazole and\/or Arene Units With Potential Bacterial and DNA Gyrase Inhibitory Potency","volume":"56","author":"Mekky A. E. M.","year":"2026","journal-title":"Synthetic Communications"},{"key":"e_1_2_8_16_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.molstruc.2025.145043","article-title":"Mrsa Inhibitory Activity of New Bis(Benzimidazole\u20101,3,4\u2010Oxadiazole) Hybrids Linked to Different Spacers: Synthesis and In Vitro Screening","volume":"1355","author":"Ahmed A. A. M.","year":"2026","journal-title":"Journal of Molecular Structure"},{"key":"e_1_2_8_17_1","doi-asserted-by":"crossref","DOI":"10.1002\/cbdv.202100500","article-title":"3\u2010Aminopyrazolo[3,4\u2010b]Pyridine: Effective Precursor for Barium Hydroxide\u2010Mediated Three Components Synthesis of New Mono\u2010 and Bis(Pyrimidines) With Potential Cytotoxic Activity","volume":"19","author":"Sanad S. M. 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E.","year":"2022","journal-title":"Journal of the Iranian Chemical Society"},{"key":"e_1_2_8_25_1","doi-asserted-by":"crossref","first-page":"4430","DOI":"10.1080\/10406638.2023.2254892","article-title":"Synthesis of New 2\u2010Pyridinone and 2\u2010Iminochromene Derivatives Bearing Biologically Active Pyrrole Moiety as Expected Antibacterial and Antifungal Agents","volume":"44","author":"Al\u2010Harbi R. A. K.","year":"2024","journal-title":"Polycyclic Aromatic Compounds"},{"key":"e_1_2_8_26_1","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1002\/jhet.3820","article-title":"Synthesis and Antioxidant Assay of New Nicotinonitrile Analogues Clubbed Thiazole, Pyrazole and\/or Pyridine Ring Systems","volume":"57","author":"Abumelha H. M. 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Flefel E.","year":"2015","journal-title":"Molecules"},{"key":"e_1_2_8_38_1","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1080\/00397911.2024.2377738","article-title":"Hantzsch Reaction: The Important Key for Pyridine\/Dihydropyridine Synthesis","volume":"54","author":"Faizan M.","year":"2024","journal-title":"Synthetic Communications"},{"key":"e_1_2_8_39_1","doi-asserted-by":"crossref","first-page":"27363","DOI":"10.1039\/D3RA04230H","article-title":"Design, Green Synthesis, and Quorum Sensing Quenching Potential of Novel 2\u2010Oxo\u2010Pyridines Containing a Thiophene\/Furan Scaffold and Targeting a Las R Gene on P. aeruginosa","volume":"13","author":"Ammar Y. 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