{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:24:19Z","timestamp":1791563059729,"version":"4.3.4"},"reference-count":19,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"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":["MicrobiologyOpen"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    is a globally prevalent protozoan parasite responsible for severe health complications, particularly in immunocompromised individuals and during congenital infections. Existing treatments are limited by suboptimal efficacy and significant side effects, highlighting the urgent need for novel therapeutic strategies. Calcium\u2010dependent protein kinase 1 (TgCDPK1) has emerged as a promising drug target due to its critical role in\n                    <jats:italic>T. gondii<\/jats:italic>\n                    pathogenesis and structural divergence from human kinases. This study integrates quantitative structure\u2013activity relationship (QSAR) modeling and molecular docking to identify and prioritize potent TgCDPK1 inhibitors. A robust QSAR model was developed from a data set of 152 ligands, leveraging a systematic feature selection process to identify 23 key molecular descriptors predictive of inhibitory activity (\n                    <jats:italic>R<\/jats:italic>\n                    \u2009=\u20090.895,\n                    <jats:italic>R<\/jats:italic>\n                    \u00b2\u2009=\u20090.802). Molecular docking studies further characterized the binding interactions of top\u2010ranked ligands, revealing strong binding affinities and favorable ADMET profiles. Notably, compound L03, identified as a substituted imidazopyrimidine derivative, demonstrated exceptional binding energy (\u2212176.794\u2009kcal\/mol) and stability within the TgCDPK1 active site. Key interactions with Asp210(A) through hydrogen bonds and hydrophobic contacts were instrumental in its high binding affinity, underscoring its potential as a lead compound. These findings provide a comprehensive framework for rational drug design, combining computational approaches to accelerate the discovery of selective and efficacious anti\u2010toxoplasma agents targeting TgCDPK1. This integrated methodology represents a significant advancement toward addressing the unmet clinical needs of toxoplasmosis treatment.\n                  <\/jats:p>","DOI":"10.1002\/mbo3.70039","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T06:21:14Z","timestamp":1753770074000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Quantitative Structure\u2013Activity Relationship Modeling and Molecular Docking Studies of TgCDPK1 Inhibitors in\n                    <i>Toxoplasma gondii<\/i>"],"prefix":"10.1002","volume":"14","author":[{"given":"Sara","family":"Lesani","sequence":"first","affiliation":[{"name":"Department of Parasitology and Mycology, School of Medicine Isfahan University of Medical Sciences Isfahan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Tavalla","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology, Faculty of Medicine Ahvaz Jundishapur University of Medical Sciences Ahvaz Iran"},{"name":"Infectious and Tropical Diseases Research Center, Health Research Institute Ahvaz Jundishapur University of Medical Sciences Ahvaz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilda","family":"Eslami","sequence":"additional","affiliation":[{"name":"Department of Parasitology and Mycology, School of Medicine Isfahan University of Medical Sciences Isfahan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2497-6158","authenticated-orcid":false,"given":"Mohammad J.","family":"Boozhmehrani","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology, Faculty of Medicine Ahvaz Jundishapur University of Medical Sciences Ahvaz Iran"},{"name":"Student Research Committee Ahvaz Jundishapur University of Medical Sciences Ahvaz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,28]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11224-019-01458-y"},{"key":"e_1_2_11_3_1","unstructured":"Aguirre T.2023. \u201cTowards Selective Kinase Inhibitors by Chemical Genetics and Photopharmacology.\u201d PhD diss. Humboldt\u2010Universit\u00e4t zu Berlin."},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-023-07936-x"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/zph.13195"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-14-487"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-32388-9"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568005024605909"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fawpar.2019.e00053"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.109176"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm201713h"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6RA20277B"},{"issue":"4","key":"e_1_2_11_13_1","first-page":"898","article-title":"Global Status of Toxoplasma gondii Infection: Systematic Review and Prevalence Snapshots","volume":"36","author":"Molan A.","year":"2019","journal-title":"Tropical Biomedical"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2020.105544"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1175409"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ipha.2024.03.001"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.6b00760"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-013-3451-y"},{"key":"e_1_2_11_19_1","doi-asserted-by":"crossref","unstructured":"Yang Y.andSun L. eds. 2024. \u201cThe Selection of the Drugs forToxoplasma gondiiand Dynamics of the Chosen Drugs.\u201d InThird International Conference on Biomedical and Intelligent Systems (IC\u2010BIS 2024). SPIE.","DOI":"10.1117\/12.3036922"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.13603"}],"container-title":["MicrobiologyOpen"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mbo3.70039","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mbo3.70039","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mbo3.70039","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T21:18:45Z","timestamp":1769721525000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mbo3.70039"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,28]]},"references-count":19,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1002\/mbo3.70039"],"URL":"https:\/\/doi.org\/10.1002\/mbo3.70039","archive":["Portico"],"relation":{},"ISSN":["2045-8827","2045-8827"],"issn-type":[{"value":"2045-8827","type":"print"},{"value":"2045-8827","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,28]]},"assertion":[{"value":"2025-02-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70039"}}