{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T01:30:58Z","timestamp":1783042258019,"version":"3.54.6"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>A newly designed benzimidazole\u2010pyridine\u2010pheylalkanesulfonate hybrids (<jats:bold>3a\u2010r<\/jats:bold>) were synthesized through the regioselective Michael addition reaction between 2\u2010acetyl\u20101\u2010substituted\u2010benzimidazole (<jats:bold>1<\/jats:bold>) and dicyano vinyl alkanesulfonate (<jats:bold>2<\/jats:bold>) to evaluate their activity against diverse microbial pathogens including <jats:italic>Candida albicans<\/jats:italic> (a unicellular fungus), <jats:italic>Bacillus subtilis<\/jats:italic> and <jats:italic>Staphylococcus aureus<\/jats:italic> (Gram\u2010positive bacteria), as well as <jats:italic>Pseudomonas aeruginosa<\/jats:italic>, <jats:italic>Klebsiella pneumoniae<\/jats:italic>, and <jats:italic>Salmonella typhimurium<\/jats:italic> (Gram\u2010negative bacteria). Although most of the tested hybrids showed promising antimicrobial potentiality, the MIC was calculated for the two precursors <jats:bold>1a<\/jats:bold>,<jats:bold>b<\/jats:bold> in addition to derivatives <jats:bold>3b<\/jats:bold>, <jats:bold>3\u2009g<\/jats:bold>, <jats:bold>3k<\/jats:bold>, <jats:bold>3\u2009m<\/jats:bold> and <jats:bold>3p<\/jats:bold> that found to prevent the proliferation of all microbial pathogens with different ratios in comparison to the reference drug used. Compound <jats:bold>3k<\/jats:bold> demonstrated the best anti\u2010candida properties with MIC\u2009=\u20095\u2009<jats:italic>\u03bc<\/jats:italic>g\/mL (amphotericin B, MIC\u2009=\u200920\u2009<jats:italic>\u03bc<\/jats:italic>g\/mL), and it was of equal efficacy to ciprofloxacin against <jats:italic>Staphylococcus aureus<\/jats:italic> with MIC\u2009=\u200920\u2009<jats:italic>\u03bc<\/jats:italic>g\/mL. Derivatives <jats:bold>3b<\/jats:bold> and <jats:bold>3\u2009m<\/jats:bold> displayed equipotent activity to ciprofloxacin with MICs\u2009=\u200910\u2009<jats:italic>\u03bc<\/jats:italic>g\/mL against <jats:italic>S. typhimurium<\/jats:italic> and <jats:italic>B. subtilis<\/jats:italic>, respectively. Moreover, derivative <jats:bold>3\u2009m<\/jats:bold> exhibited 42.1% biofilm inhibition against <jats:italic>P. aeruginosa<\/jats:italic> (compared with 39.8% for Ciprofloxacin). An acceptable safety profile of the most potent derivatives was detected. The impact of the <jats:bold>3b<\/jats:bold> and <jats:bold>3k<\/jats:bold> hybrids on the tested microbial pathogens was visualized using CLSM. Furthermore, <jats:bold>3k<\/jats:bold> inhibited the Lanosterol 14\u03b1\u2010demethylase (CYP51) with IC<jats:sub>50<\/jats:sub>\u2009=\u20094.2\u2009<jats:italic>\u03bc<\/jats:italic>M (fluconazole IC<jats:sub>50<\/jats:sub>\u2009=\u20090.6\u2009<jats:italic>\u03bc<\/jats:italic>M). Furthermore, in silico studies including ADME prediction for the five promising hits and molecular docking simulation of <jats:bold>3k<\/jats:bold> in the demethylase binding site were performed.<\/jats:p>","DOI":"10.1002\/ddr.70122","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T02:38:59Z","timestamp":1750732739000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Novel Benzimidazole\u2010Pyridine\u2010Phenylalkanesulfonate Hybrids: Design, Synthesis, Antimicrobial Screening, Lanosterol 14\u03b1\u2010Demethylase Inhibition Properties and in Silico Studies"],"prefix":"10.1002","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9219-5436","authenticated-orcid":false,"given":"Aisha A. K.","family":"Al\u2010Ashmawy","sequence":"first","affiliation":[{"name":"Department of Therapeutic Chemistry, Pharmaceutical and Drug Industries Research Institute National Research Centre, Dokki Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Abdelraof","sequence":"additional","affiliation":[{"name":"Microbial Chemistry Department, Biotechnology Research Institute National Research Centre Dokki Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6286-319X","authenticated-orcid":false,"given":"Asmaa","family":"Saleh","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy Princess Nourah bint Abdulrahman University Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6692-6952","authenticated-orcid":false,"given":"Aladdin M.","family":"Srour","sequence":"additional","affiliation":[{"name":"Department of Therapeutic Chemistry, Pharmaceutical and Drug Industries Research Institute National Research Centre, Dokki Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2023.106538"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2023.106538"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2024.138224"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26144112"},{"key":"e_1_2_9_6_1","first-page":"605","volume-title":"Recent Developments in the Synthesis and Applications of Pyridines","author":"Allaka T. 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