{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:04:30Z","timestamp":1791615870494,"version":"4.3.4"},"reference-count":31,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,28]],"date-time":"2024-01-28T00:00:00Z","timestamp":1706400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Activated blood coagulation factor X (FXa) plays a critical initiation step of the blood-coagulation pathway and is considered a desirable target for anticoagulant drug development. It is reversibly inhibited by nonvitamin K antagonist oral anticoagulants (NOACs) such as apixaban, betrixaban, edoxaban, and rivaroxaban. Thrombosis is extremely common and is one of the leading causes of death in developed countries. In previous studies, novel thiourea and oxime ether isosteviol derivatives as FXa inhibitors were designed through a combination of QSAR studies and molecular docking. In the present contribution, molecular dynamics (MD) simulations were performed for 100 ns to assess binding structures previously predicted by docking and furnish additional information. Moreover, three thiourea- and six oxime ether-designed isosteviol analogs were then examined for their drug-like and ADMET properties. MD simulations demonstrated that four out of the nine investigated isosteviol derivatives, i.e., one thiourea and three oxime ether ISV analogs, form stable complexes with FXa. These derivatives interact with FXa in a manner similar to Food and Drug Administration (FDA)-approved drugs like edoxaban and betrixaban, indicating their potential to inhibit factor Xa activity. One of these derivatives, E24, displays favorable pharmacokinetic properties, positioning it as the most promising drug candidate. This, along with the other three derivatives, can undergo further chemical synthesis and bioassessment.<\/jats:p>","DOI":"10.3390\/ph17020163","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T08:11:27Z","timestamp":1706515887000},"page":"163","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Novel Thiourea and Oxime Ether Isosteviol-Based Anticoagulants: MD Simulation and ADMET Prediction"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9176-7108","authenticated-orcid":false,"given":"Marcin","family":"Gackowski","sequence":"first","affiliation":[{"name":"Department of Toxicology and Bromatology, Faculty of Pharmacy, L. Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, A. Jurasza 2 Street, 85089 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9832-4786","authenticated-orcid":false,"given":"Mateusz","family":"J\u0119drzejewski","sequence":"additional","affiliation":[{"name":"Department of Organic and Physical Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1 Street, 02093 Warsaw, Poland"},{"name":"Doctoral School, Medical University of Warsaw, \u017bwirki i Wigury 81 Street, 02093 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sri Satya","family":"Medicharla","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M. S. Ramaiah University of Applied Sciences, Bengaluru 560054, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh","family":"Kondabala","sequence":"additional","affiliation":[{"name":"Thapar Institute of Engineering and Technology, Patiala 147004, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6918-319X","authenticated-orcid":false,"given":"Burhanuddin","family":"Madriwala","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M. S. Ramaiah University of Applied Sciences, Bengaluru 560054, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"M\u0105dra-Gackowska","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Faculty of Health Sciences, L. Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Sk\u0142odowskiej Curie 9 Street, 85094 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5853-4214","authenticated-orcid":false,"given":"Renata","family":"Studzi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Pharmacy, L. Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, A. Jurasza 2 Street, 85089 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mari\u00f1o-Ocampo, N., Rodr\u00edguez, D.F., Guerra D\u00edaz, D., Z\u00fa\u00f1iga-N\u00fa\u00f1ez, D., Duarte, Y., Fuentealba, D., and Zacconi, F.C. (2023). 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