{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T13:19:44Z","timestamp":1773494384924,"version":"3.50.1"},"reference-count":56,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"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":["Chemistry &amp;amp; Biodiversity"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This study investigates the value addition of\n                    <jats:italic>Citrus maxima<\/jats:italic>\n                    fruit peels by extracting Naringenin and chemically modifying it into hydrazone derivatives to enhance its anti\u2010cancer and anti\u2010osteoporotic potential. The compounds (\n                    <jats:bold>2a<\/jats:bold>\n                    \u2013\n                    <jats:bold>f<\/jats:bold>\n                    ) were synthesised using simple and efficient chemistry. Their pharmacokinetic properties, molecular docking and simulations were evaluated against key hormonal targets, EGFR, ER\u03b1, ER\u03b2, HER2 and PR. The cytotoxicity of the compounds was assessed against MCF\u20107 and SiHa cell lines using MTT assay, while their osteogenic potential was evaluated using osteoblast differentiation and bone mineralization assays. Amongst other compounds,\n                    <jats:bold>2d<\/jats:bold>\n                    and\n                    <jats:bold>2f<\/jats:bold>\n                    exhibited significant anti\u2010breast cancer activity, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 36 and 20\u00a0\u00b5M, respectively. Fluorinated derivative\n                    <jats:bold>2d<\/jats:bold>\n                    demonstrated a strong osteogenic effect by enhancing osteoblast differentiation at 10 and 100\u00a0nM concentrations and significant bone mineralization, along with anti\u2010breast cancer properties, potentially due to its distinct physicochemical characteristics, including a small atomic radius and high electronegativity. Importantly, the synthesized compounds showed no inherent toxicity toward non\u2010cancerous HEK 293 cells and healthy osteoblasts. Molecular docking studies revealed improved ER\u03b1 binding, further validated by 100\u00a0ns molecular dynamics simulations. SwissADME analysis confirmed favourable physicochemical properties, supporting the drug\u2010like potential of these derivatives.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202501059","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T19:59:02Z","timestamp":1754683142000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Value Addition to\n                    <i>Citrus maxima<\/i>\n                    Peels: Extraction and Modification of Naringenin into Hydrazones Derivatives for Anti\u2010Breast Cancer and Osteogenic Activity via In Vitro and In Silico Studies"],"prefix":"10.1002","volume":"22","author":[{"given":"Akrati","family":"Sant","sequence":"first","affiliation":[{"name":"Department of Chemistry Isabella Thoburn College University of Lucknow  Lucknow India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shristi","family":"Modanwal","sequence":"additional","affiliation":[{"name":"Department of Applied Sciences Indian Institute of Information Technology  Allahabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shama","family":"Parveen","sequence":"additional","affiliation":[{"name":"Molecular and Human Genetics Laboratory Department of Zoology University of Lucknow  Lucknow India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Ahtsham","sequence":"additional","affiliation":[{"name":"Molecular and Human Genetics Laboratory Department of Zoology University of Lucknow  Lucknow India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konica","family":"Porwal","sequence":"additional","affiliation":[{"name":"Division of Endocrinology CSIR\u2010Central Drug Research Institute  Lucknow India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nidhi","family":"Mishra","sequence":"additional","affiliation":[{"name":"Department of Applied Sciences Indian Institute of Information Technology  Allahabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monisha","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Molecular and Human Genetics Laboratory Department of Zoology University of Lucknow  Lucknow India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naibedya","family":"Chattopadhyay","sequence":"additional","affiliation":[{"name":"Division of Endocrinology CSIR\u2010Central Drug Research Institute  Lucknow India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atul","family":"Gupta","sequence":"additional","affiliation":[{"name":"Phytochemistry Division CSIR\u2010Central Institute of Medicinal and Aromatic Plants  Lucknow India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8510-2695","authenticated-orcid":false,"given":"Sonika","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Department of Chemistry Isabella Thoburn College University of Lucknow  Lucknow India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871520617666170912121422"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/01635581.2013.756920"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tifs.2011.05.004"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/903603"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12199\u2010018\u20100724\u20101"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2891-4-30"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.6061\/clinics\/2012(07)13"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.2174\/1573408011666150730204108"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/plants6040042"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2021.12.007"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2016.05.026"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.10.124"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1121950"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/13697137.2020.1863356"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114850"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01614"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28104121"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1515\/gps\u20102017\u20100112"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10068\u2010024\u201001773\u2010z"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2022.120752"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2005.05.001"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/plants9121784"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-016-5013-2"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/4724920"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.14084"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2022.108967"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-018-00556-3"},{"issue":"6","key":"e_1_2_9_29_1","first-page":"2895","article-title":"Estradiol 17 \u03b2\u2010Hydroxysteroid Dehydrogenase, a Marker of Breast Cancer Hormone Dependency","volume":"45","author":"Fournier S.","year":"1985","journal-title":"Cancer Research"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2016.01.010"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.4103\/0975-7406.129170"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf2017594"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms13022025"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2020.115798"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010023\u201005905\u2010z"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2014.06.012"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2007.10.006"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.saa.2011.09.066"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202401561"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2025.117380"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2014.03.002"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b01788"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfluchem.2016.12.016"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26040989"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25063341"},{"issue":"6","key":"e_1_2_9_46_1","first-page":"3147","article-title":"The Story of MCF\u20107 Breast Cancer Cell Line: 40 Years of Experience in Research","volume":"35","author":"Com\u015fa \u015e.","year":"2015","journal-title":"Anticancer Research"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/0039\u2010128x(75)90110\u20105"},{"key":"e_1_2_9_48_1","first-page":"85","volume-title":"Breast Cancer\u2014Focusing Tumor Microenvironment, Stem cells and Metastasis","author":"Shirazi F. H.","year":"2011"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1088\/1757\u2010899x\/1263\/1\/012031"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imu.2022.100894"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jics.2022.100790"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2021.130733"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemphys.2023.112053"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2023.123212"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfu020"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2016.02.002"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.434"}],"container-title":["Chemistry &amp; Biodiversity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbdv.202501059","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbdv.202501059","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbdv.202501059","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T11:54:35Z","timestamp":1773489275000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cbdv.202501059"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,8]]},"references-count":56,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/cbdv.202501059"],"URL":"https:\/\/doi.org\/10.1002\/cbdv.202501059","archive":["Portico"],"relation":{},"ISSN":["1612-1872","1612-1880"],"issn-type":[{"value":"1612-1872","type":"print"},{"value":"1612-1880","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,8]]},"assertion":[{"value":"2025-03-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01059"}}