{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T22:00:27Z","timestamp":1791583227882,"version":"4.3.4"},"reference-count":56,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007446","name":"King Khalid University","doi-asserted-by":"crossref","award":["RGP-2\/233\/46"],"award-info":[{"award-number":["RGP-2\/233\/46"]}],"id":[{"id":"10.13039\/501100007446","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Epilepsy is characterized by unpredictable seizures and drug resistance, along with rising antimicrobial resistance (AMR), highlighting the urgent need for innovative dual-action therapies. This study aimed to design, develop, and evaluate novel pyrazolone derivatives for a dual antimicrobial and antiepileptic potential. Methods: Novel pyrazolone derivatives were designed, synthesized (using 2,4-dinitrophenylhydrazine\/semicarbazide condensation with ethyl acetoacetate), and evaluated through molecular docking against antimicrobial (4URM, 3FYV, 3FRA) and neuronal targets (4COF, 5TP9, 5L1F). The in vitro antimicrobial activity was assessed against Gram-positive (S. aureus) and in vitro Gram-negative (E. coli, P. aeruginosa) strains via agar cup plate assays, while in vivo antiepileptic efficacy was tested in a PTZ-induced seizure model in Swiss albino mice. Results: Compound IIa showed potent dual activity, inhibiting E. coli (9 mm zone at 80 \u03bcg\/mL) and S. aureus (9.5 mm at 80 \u03bcg\/mL), alongside a significantly delayed seizure onset in the PTZ-induced mouse model (100% survival rate, 45 sec delayed seizure onset, p &lt; 0.001). Compounds Ia and Id showed selective activity against E. coli (6 mm at 80 \u03bcg\/mL) and P. aeruginosa (7 mm at 80 \u03bcg\/mL), respectively. Docking studies revealed that compound IIa has a superior binding affinity (\u22127.57 kcal\/mol for 3FYV) compared to standards, driven by hydrogen bonds (SER X: 49) and hydrophobic interactions (LEU X: 20). Conclusions: This study presents a novel approach by proposing a rationally designed pyrazolone scaffold exhibiting both antimicrobial and antiepileptic activity, which integrates in silico modeling with experimental validation. Compound IIa emerged with preliminary dual biological activities, exhibiting strong antibacterial activity, a superior binding affinity toward both bacterial and neuronal targets, and notable seizure prevention in vivo. These findings show the potential of multifunctional pyrazolone derivatives as a new treatment strategy for addressing drug-resistant infections linked to epilepsy and support further optimization toward clinical development.<\/jats:p>","DOI":"10.3390\/ph19020193","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T13:55:34Z","timestamp":1769176534000},"page":"193","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Design, Docking, Synthesis, and Biological Evaluation of Pyrazolone Derivatives as Potential Dual-Action Antimicrobial and Antiepileptic Agents"],"prefix":"10.3390","volume":"19","author":[{"given":"Yousef","family":"Al-ebini","sequence":"first","affiliation":[{"name":"Department of Cosmetic Science, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman 19328, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8850-7110","authenticated-orcid":false,"given":"Manojmouli","family":"Chandramouli","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, B. G. Nagara 571448, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3269-3094","authenticated-orcid":false,"given":"Naga Prashant","family":"Koppuravuri","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, B. G. Nagara 571448, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0385-3343","authenticated-orcid":false,"given":"Thoppalada Yunus","family":"Pasha","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, B. G. Nagara 571448, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8826-3718","authenticated-orcid":false,"given":"Mohamed","family":"Rahamathulla","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62223, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salwa","family":"Eltawaty","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Faculty of Pharmacy, Omar Al-Mukhtar University, Albayda P.O. Box 991, Libya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4064-8544","authenticated-orcid":false,"given":"Kamal Y.","family":"Thajudeen","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha 61421, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Muqtader","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdul Aziz University, Al Kharj 11942, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thippeswamy Boreddy","family":"Shivanandappa","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, College of Pharmacy, Shaqra University, Al-Dawadmi Campus, Dawadmi 11961, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez Garc\u00eda, E., Lambert Lamazares, B., G\u00f3mez-Lira, G., Mendoza-Torreblanca, J.G., Duke Lomeli, P., L\u00f3pez Flores, Y., Rangel Escobar, L.E., Mej\u00eda Arangur\u00e9, E., Ruiz-Velasco Acosta, S., and Naranjo Albarr\u00e1n, L. 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