{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:58:08Z","timestamp":1787029088788,"version":"build-2736575974"},"reference-count":39,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T00:00:00Z","timestamp":1689206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King Saud University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The development of novel scaffolds that can increase the effectiveness, safety, and convenience of medication therapy using drug conjugates is a promising strategy. As a result, drug conjugates are an active area of research and development in medicinal chemistry. This research demonstrates acetamide\u2013sulfonamide scaffold preparation after conjugation of ibuprofen and flurbiprofen with sulfa drugs, and these scaffolds were then screened for urease inhibition. The newly designed conjugates were confirmed by spectroscopic techniques such as IR, 1HNMR, 13CNMR, and elemental analysis. Ibuprofen conjugated with sulfathiazole, flurbiprofen conjugated with sulfadiazine, and sulfamethoxazole were found to be potent and demonstrated a competitive mode of urease inhibition, with IC50 (\u00b5M) values of 9.95 \u00b1 0.14, 16.74 \u00b1 0.23, and 13.39 \u00b1 0.11, respectively, and urease inhibition of 90.6, 84.1, and 86.1% respectively. Ibuprofen conjugated with sulfanilamide, sulfamerazine, and sulfacetamide, whereas flurbiprofen conjugated with sulfamerazine, and sulfacetamide exhibited a mixed mode of urease inhibition. Moreover, through molecular docking experiments, the urease receptor-binding mechanisms of competitive inhibitors were anticipated, and stability analysis through MD simulations showed that these compounds made stable complexes with the respective targets and that no conformational changes occurred during the simulation. The findings demonstrate that conjugates of approved therapeutic molecules may result in the development of novel classes of pharmacological agents for the treatment of various pathological conditions involving the urease enzyme.<\/jats:p>","DOI":"10.3390\/molecules28145389","type":"journal-article","created":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T00:49:30Z","timestamp":1689295770000},"page":"5389","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["New Acetamide-Sulfonamide-Containing Scaffolds: Antiurease Activity Screening, Structure-Activity Relationship, Kinetics Mechanism, Molecular Docking, and MD Simulation Studies"],"prefix":"10.3390","volume":"28","author":[{"given":"Saghir","family":"Ahmad","sequence":"first","affiliation":[{"name":"School of Chemistry, University of the Punjab, Lahore 54590, Pakistan"},{"name":"Department of Microbiology, Immunology and Cancer Biology, School of Medicine, University of Virginia, Charlottesville, VA 22904, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Abdul Qadir","sequence":"additional","affiliation":[{"name":"School of Chemistry, University of the Punjab, Lahore 54590, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2285-7406","authenticated-orcid":false,"given":"Mahmood","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Division of Science and Technology, University of Education, College Road, Lahore 54770, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0863-9637","authenticated-orcid":false,"given":"Muhammad","family":"Imran","sequence":"additional","affiliation":[{"name":"Kauser Abdulla Malik School of Life Sciences, Forman Christian College (A Chartered University), Lahore 54600, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2783-7823","authenticated-orcid":false,"given":"Numan","family":"Yousaf","sequence":"additional","affiliation":[{"name":"Department of Biosciences, COMSATS University Islamabad, Park Road, Islamabad 45550, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3498-4112","authenticated-orcid":false,"given":"Tanveer A.","family":"Wani","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5622-0841","authenticated-orcid":false,"given":"Seema","family":"Zargar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Science, King Saud University, P.O. Box 222452, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ijaz","family":"Ali","sequence":"additional","affiliation":[{"name":"Center for Applied Mathematics and Bioinformatics, Gulf University for Science and Technology, Mubarak Al-Abdullah 32093, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Muddassar","sequence":"additional","affiliation":[{"name":"Department of Biosciences, COMSATS University Islamabad, Park Road, Islamabad 45550, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tirmazi, S.A.A.S., Qadir, M.A., Ahmed, M., Imran, M., Hussain, R., Sharif, M., Yousaf, M., and Muddassar, M. (2021). Levofloxacin and sulfa drugs linked via schiff bases: Exploring their urease inhibition, enzyme kinetics and in silico studies. J. Mol. 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