{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T03:25:52Z","timestamp":1788492352941,"version":"build-2803163510"},"reference-count":80,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T00:00:00Z","timestamp":1733443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002713","name":"Deanship of Scientific Research at Imam Mohammad Ibn Saud Islamic University (IMSIU)","doi-asserted-by":"publisher","award":["IMSIU-RP23031"],"award-info":[{"award-number":["IMSIU-RP23031"]}],"id":[{"id":"10.13039\/501100002713","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In response to the escalating crisis of antimicrobial resistance (AMR), there is an urgent need to research and develop novel antibiotics. This study presents the synthesis and assessment of innovative 4-aminoquinoline-benzohydrazide-based molecular hybrids bearing aryl aldehydes (HD1-23) and substituted isatin warheads (HS1-12), characterized using multispectroscopic techniques with high purity confirmed by HRMS. The compounds were evaluated against a panel of clinically relevant antibacterial strains including the Gram-positive Enterococcus faecium, Bacillus subtilis, and Staphylococcus aureus and a Gram-negative Pseudomonas aeruginosa bacterial strain. Preliminary screenings revealed that several test compounds had significant antimicrobial effects, with HD6 standing out as a promising compound. Additionally, HD6 demonstrated impressively low minimum inhibitory concentrations (MICs) in the range of (8\u2013128 \u03bcg\/mL) against the strains B. subtilis,\u00a0S. aureus and P. aeruginosa. Upon further confirmation, HD6 not only showed bactericidal properties with low minimum bactericidal concentrations (MBCs) such as (8 \u03bcg\/mL against B. subtilis) but also displayed a synergistic effect when combined with the standard drug ciprofloxacin (CIP), highlighted by its FICI value of (0.375) against P. aeruginosa, while posing low toxicity risk. Remarkably, HD6 also inhibited a multidrug-resistant (MDR) bacterial strain, marking it as a critical addition to our antimicrobial arsenal. Computation studies were performed to investigate the possible mechanism of action of the most potent hybrid HD6 on biofilm-causing protein (PDB ID: 7C7U). The findings suggested that HD6 exhibits favorable binding free energy, which is supported by the MD simulation studies, presumably responsible for the bacterial growth inhibition. Overall, this study provides a suitable core for further synthetic alterations for their optimization as an antibacterial agent.<\/jats:p>","DOI":"10.3390\/molecules29235777","type":"journal-article","created":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T10:58:45Z","timestamp":1733482725000},"page":"5777","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Synthesis and Structure\u2013Activity Relationship (SAR) Studies on New 4-Aminoquinoline-Hydrazones and Isatin Hybrids as Promising Antibacterial Agents"],"prefix":"10.3390","volume":"29","author":[{"given":"Ayesha","family":"Ubaid","sequence":"first","affiliation":[{"name":"Medicinal Chemistry Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd.","family":"Shakir","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1574-4796","authenticated-orcid":false,"given":"Asghar","family":"Ali","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India"},{"name":"Clinical Biochemistry Laboratory, Department of Biochemistry, School of Chemical and Life Science, Jamia Hamdard, New Delhi 110062, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sobia","family":"Khan","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihad","family":"Alrehaili","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 13317-4233, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9223-1951","authenticated-orcid":false,"given":"Razique","family":"Anwer","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 13317-4233, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0507-8451","authenticated-orcid":false,"given":"Mohammad","family":"Abid","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Muteeb, G., Rehman, M.T., Shahwan, M., and Aatif, M. 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