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Bisphosphonates and Vitamin D are commonly administered drugs for the treatment of bone diseases and the prevention of bone metastases. Platinum\u2010based and methotrexate are widely used anticancer drugs in clinics. However, their use is hampered by adverse side effects. Hybrid\u2010based compounds containing either bisphosphonate, vitamin D, platinum\u2010based, or methotrexate were synthesized and characterized using FTIR, <jats:sup>1<\/jats:sup>H\u2010,<jats:sup>31<\/jats:sup>P, <jats:sup>13<\/jats:sup>C\u2010NMR, and UHPLC\u2010HRMS which confirmed their successful synthesis. The hydroxyapatite bone binding assay revealed a promising percentage binding affinity of the bisphosphonate hybrid compounds. <jats:italic>In vitro<\/jats:italic> cytotoxicity assays on MCF\u20107 and HT\u201029\u2005cell lines revealed a promising cytotoxic effect of hybrid <jats:bold>19<\/jats:bold> at 50 and 100\u2005\u03bcg\/mL on HT\u201029 and hybrid <jats:bold>15<\/jats:bold> on MCF\u20107 at 100\u2005\u03bcg\/mL. Molecular docking and dynamics simulation analysis revealed a binding affinity of \u22129.70\u2005kcal\/mol for hybrid <jats:bold>15<\/jats:bold> against Human 3 alpha\u2010hydroxysteroid dehydrogenase type 3, showing its capability to inhibit Human 3 alpha\u2010hydroxysteroid dehydrogenase type 3. The Swiss ADME, ProTox\u2010II, GUSAR (General Unrestricted Structure\u2010Activity Relationships), and molecular docking and dynamics studies revealed that these compounds are promising anticancer compounds.<\/jats:p>","DOI":"10.1002\/cbdv.202400373","type":"journal-article","created":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T02:23:47Z","timestamp":1726453427000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Hybrid Molecules Containing Methotrexate, Vitamin D, and Platinum Derivatives: Synthesis, Characterization, <i>In Vitro<\/i> Cytotoxicity, <i>In Silico<\/i> ADME Docking, Molecular Docking and Dynamics"],"prefix":"10.1002","volume":"22","author":[{"given":"Zintle","family":"Mbese","sequence":"first","affiliation":[{"name":"Department of Chemistry University of Fort Hare  Alice Campus 5700 Alice, Eastern Cape South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mpho","family":"Choene","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Johannesburg  Kingsway Campus, Auckland Park 2006 Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Morifi","sequence":"additional","affiliation":[{"name":"School of Chemistry Mass Spectrometry Division University of Witwatersrand  2050 Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Nwamadi","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Johannesburg  Auckland Park Campus 2006 Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samson","family":"Adeyemi","sequence":"additional","affiliation":[{"name":"Wits Advanced Drug Delivery Platform Research Unit Department of Pharmacy and Pharmacology School of Therapeutic Science Faculty of Health Sciences University of the Witwatersrand  Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2318-8208","authenticated-orcid":false,"given":"Abel","family":"Kolawole Oyebamiji","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Industrial Chemistry Bowen University  Iwo, Osun State Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adedapo S.","family":"Adeyinka","sequence":"additional","affiliation":[{"name":"Research Centre for Synthesis and Catalysis Department of Chemical Sciences University of Johannesburg  Auckland Park 2006 Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blassan","family":"George","sequence":"additional","affiliation":[{"name":"Laser Research Centre, Faculty of Health Sciences University of Johannesburg  Doornfontein Campus 2028 Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1157-7481","authenticated-orcid":false,"given":"Blessing Atim","family":"Aderibigbe","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Fort Hare  Alice Campus 5700 Alice, Eastern Cape South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,7]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-015-1329-4"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000358258"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2011.05.009"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2022.116652"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cclet.2018.02.010"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2011.10.019"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2013.06.001"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b00208"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbo.2016.02.004"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2014.12.033"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-62039-2"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21103483"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25246049"},{"key":"e_1_2_8_14_1","first-page":"618","volume":"71","author":"Kmiecik S. 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