{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T04:59:12Z","timestamp":1785214752349,"version":"3.55.0"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background and purpose:<\/jats:title>\n                    <jats:p>Breast cancer remains the most commonly diagnosed cancer and the leading cause of cancer-related death among women worldwide. Estrogen receptor alpha (ER\u03b1) plays a major role in breast cancer cell proliferation, and approximately 70-80% of breast cancer cases are classified as Er\u03b1-positive. This study aims to predict the pinostrobin pentanoate potential against ER\u03b1 by docking and molecular dynamics, and determine its cytotoxic activity against T47D breast cancer cells and normal cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental approach:<\/jats:title>\n                    <jats:p>Docking was analyzed using MOE 2022.02. Furthermore, AMBER 20 was used for molecular dynamics. Cytotoxicity was assessed using the MTT assay against T47D breast cancer cells and Vero cells for its selectivity index (SI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings\/Results:<\/jats:title>\n                    <jats:p>\n                      Based on docking results, the binding free energy of pinostrobin pentanoate (-7.682 \u00b1 0.145 kcal\/mol) was lower compared to pinostrobin (-6.503 \u00b1 0.153 kcal\/mol) against ER\u03b1, indicating the stronger binding affinity. In addition, the stability interaction using 100 ns molecular dynamics showed a stable interaction. Moreover, the IC\n                      <jats:sub>50<\/jats:sub>\n                      values of pinostrobin and pinostrobin pentanoate against T47D cells were 160 \u00b1 5.30 \u03bcM and 32 \u00b1 3.64 \u03bcM, respectively, compared to doxorubicin 0.14 \u00b1 0.04 \u03bcM. Meanwhile, the CC\n                      <jats:sub>50<\/jats:sub>\n                      values of pinostrobin and pinostrobin pentanoate from the cytotoxicity test on Vero cells were estimated to be &gt; 2500 and &gt; 1500 \u03bcM, respectively. Therefore, the SI value of pinostrobin (SI &gt; 15.6) is estimated to be smaller than that of pinostrobin pentanoate (SI &gt; 46.8). Additionally, the combination of pinostrobin pentanoate and doxorubicin showed synergistic efficacy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and implications:<\/jats:title>\n                    <jats:p>Pinostrobin pentanoate is more selective than pinostrobin, and it can be used as an anti-breast cancer candidate against the ER\u03b1 for further research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/rps.rps_108_25","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T04:00:28Z","timestamp":1785124828000},"page":"466-480","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Pinostrobin pentanoate as a selective estrogen receptor-\u03b1 antagonist in breast cancer: integrated in silico and in vitro evaluation"],"prefix":"10.4103","volume":"21","author":[{"given":"Tri","family":"Widiandani","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya 60115, Indonesia"},{"name":"Research Group of Drug Development, Faculty of Pharmacy, Universitas Airlangga, Surabaya 60115, Indonesia"},{"name":"Inter-University Center of Excellence (IUCoE) of Health Autonomy-Drug Discovery, Universitas Airlangga, Surabaya 60115, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delis","family":"Susilawati","sequence":"additional","affiliation":[{"name":"Master Program of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya 60115, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ave","family":"Rahman","sequence":"additional","affiliation":[{"name":"Master Program of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya 60115, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siti","family":"Rahmah","sequence":"additional","affiliation":[{"name":"Master Program of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya 60115, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanny Ika","family":"Sulistyowaty","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya 60115, Indonesia"},{"name":"Research Group of Drug Development, Faculty of Pharmacy, Universitas Airlangga, Surabaya 60115, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Mu\u2019thi Andy","family":"Suryadi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Sports and Health, Universitas Negeri Gorontalo, Gorontalo 96128, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bambang Tri","family":"Purwanto","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya 60115, Indonesia"},{"name":"Research Group of Drug Development, Faculty of Pharmacy, Universitas Airlangga, Surabaya 60115, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siswandono","family":"Siswodihardjo","sequence":"additional","affiliation":[{"name":"Research Group of Drug Development, Faculty of Pharmacy, Universitas Airlangga, Surabaya 60115, Indonesia"},{"name":"Faculty of Pharmacy, Institut Ilmu Kesehatan Bhakti Wiyata, Kediri 64114, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"issue":"6","key":"R2-20260728","first-page":"394","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J Clin"},{"key":"R3-20260728","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.breast.2022.08.010","article-title":"Current and future burden of breast cancer: global statistics for 2020 and 2040","volume":"66","author":"Arnold","year":"2022","journal-title":"Breast,"},{"issue":"13","key":"R4-20260728","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1021\/acs.jmedchem.3c00136","article-title":"Targeting the estrogen receptor for the treatment of breast cancer: recent advances and challenges","volume":"66","author":"Rej","year":"2023","journal-title":"J Med Chem"},{"issue":"19","key":"R5-20260728","doi-asserted-by":"crossref","first-page":"4689","DOI":"10.3390\/cancers15194689","article-title":"Estrogen receptor signaling in breast cancer","volume":"15","author":"Miziak","year":"2023","journal-title":"Cancers (Basel)"},{"issue":"11","key":"R6-20260728","doi-asserted-by":"crossref","first-page":"2966","DOI":"10.3390\/cells10112966","article-title":"Positive regulation of estrogen receptor alpha in breast tumorigenesis","volume":"10","author":"Porras","year":"2021","journal-title":"Cells"},{"issue":"4","key":"R7-20260728","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1016\/j.gendis.2022.02.007","article-title":"Cancer chemotherapy and beyond: current status, drug candidates, associated risks and progress in targeted therapeutics","volume":"10","author":"Anand","year":"2023","journal-title":"Genes Dis"},{"issue":"1","key":"R8-20260728","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1007\/s12672-024-00993-3","article-title":"Drug resistance in breast cancer is based on the mechanism of exocrine non-coding RNA","volume":"15","author":"Ye","year":"2024","journal-title":"Discov Onc"},{"issue":"4","key":"R10-20260728","doi-asserted-by":"crossref","first-page":"289","DOI":"10.2174\/1568009621666210203111220","article-title":"Flavonoids overcome drug resistance to cancer chemotherapy by epigenetically modulating multiple mechanisms","volume":"21","author":"To","year":"2021","journal-title":"Curr Cancer Drug Targets"},{"issue":"4","key":"R11-20260728","first-page":"1","article-title":"Molecular dynamics of pinostrobin and pinocembrin from Kaempferia pandurata Roxb. towards estrogen receptor positive (ESR) and estrogen receptor negative (VEGFR) of breast cancer","volume":"12","author":"Fadilah","year":"2018","journal-title":"Asian J Pharm"},{"issue":"6","key":"R12-20260728","doi-asserted-by":"crossref","first-page":"2797","DOI":"10.5958\/0974-360X.2020.00497.7","article-title":"Isolation, synthesis nanoparticle, and in-vitro test of pinostrobin from Kaempferia pandurata on MCF-7 and MDAMB-231 breast cancer cell","volume":"13","author":"Wiyono","year":"2020","journal-title":"Res J Pharm Technol"},{"issue":"4","key":"R13-20260728","doi-asserted-by":"crossref","first-page":"2559","DOI":"10.31788\/RJC.2020.1345749","article-title":"Molecular modeling, synthesis, and QSAR of 5-o-acylpinostrobin derivatives as promising analgesic agent","volume":"13","author":"Siswandono,","year":"2020","journal-title":"Rasayan J Chem"},{"issue":"3","key":"R14-20260728","doi-asserted-by":"crossref","first-page":"51","DOI":"10.46542\/pe.2024.243.5156","article-title":"Pinostrobin and its derivatives as novel anti-breast cancer agents against human oestrogen receptor alpha: in silico studies of ADMET, docking, and molecular dynamics","volume":"24","author":"Susilawati","year":"2024","journal-title":"Pharm Educ"},{"issue":"Suppl 1","key":"R15-20260728","first-page":"2516","article-title":"In vitro study of pinostrobin propionate and pinostrobin butyrate: cytotoxic activity against breast cancer cell T47D and its selectivity index","volume":"14","author":"Widiandani","year":"2023","journal-title":"J Public Health Afr"},{"key":"R16-20260728","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.csbj.2018.10.003","article-title":"Towards good correlation between fragment molecular orbital interaction energies and experimental IC50 for ligand binding: a case study of p38 MAP kinase","volume":"16","author":"Sheng","year":"2018","journal-title":"Comput Struct Biotechnol J"},{"issue":"2","key":"R17-20260728","doi-asserted-by":"crossref","first-page":"177","DOI":"10.12928\/pharmaciana.v8i2.8993","article-title":"In silico study of the active compounds in bitter melon (Momordica charantia L) as antidiabetic medication","volume":"8","author":"Ruswanto","year":"2018","journal-title":"Pharmaciana,"},{"issue":"2","key":"R18-20260728","doi-asserted-by":"crossref","first-page":"65","DOI":"10.24198\/ijpst.v6i2.18168","article-title":"Molecular dynamics simulation estrogen receptor alpha against andrographolide as anti-breast cancer","volume":"6","author":"Dermawan","year":"2019","journal-title":"Indonesian J Pharm Sci and Tech"},{"issue":"16","key":"R19-20260728","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1002\/jcc.10128","article-title":"Fast, efficient generation of high-quality atomic charges. AM1-BCC model: II. Parameterization and validation","volume":"23","author":"Jakalian","year":"2002","journal-title":"J Comput Chem"},{"issue":"2","key":"R20-20260728","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1002\/wcms.1121","article-title":"An overview of the Amber biomolecular simulation package","volume":"3","author":"Salomon-Ferrer","year":"2013","journal-title":"WIREs Comput Mol Sci"},{"issue":"12","key":"R21-20260728","doi-asserted-by":"crossref","first-page":"5754","DOI":"10.1021\/acs.jcim.0c00326","article-title":"Discovery of new hydroxyethylamine analogs against 3CLpro protein target of SARS-CoV-2: molecular docking, molecular dynamics simulation, and structure-activity relationship studies","volume":"60","author":"Kumar","year":"2020","journal-title":"J Chem Inf Model"},{"issue":"2","key":"R22-20260728","first-page":"1909","article-title":"Docking and Cytotoxicity Test on Human Breast Cancer Cell Line (T47D) of N-(Allylcarbamothioyl)-3-chlorobenzamide and N-(Allylcarbamothioyl)-3, 4-dichlorobenzamide","volume":"8","author":"Widiandani","year":"2017","journal-title":"Res J Pharm Biol Chem Sci"},{"issue":"8","key":"R23-20260728","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.4314\/tjpr.v17i8.20","article-title":"New N-allylthiourea derivatives: synthesis, molecular docking and in vitro cytotoxicity studies","volume":"17","author":"Widiandani","year":"2018","journal-title":"Tropical J Pham Res"},{"issue":"3","key":"R24-20260728","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.31788\/RJC.2022.1536976","article-title":"The potency of 4-nitrobenzoyl-3-allylthiourea as an agent of breast cancer with EGFR\/HER2: in silico and in vitro study","volume":"15","author":"Widiandani","year":"2022","journal-title":"Rasayan J Chem"},{"key":"R25-20260728","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1002\/fft2.44","article-title":"Guidelines for cell viability assays","volume":"1","author":"Kamiloglu","year":"2020","journal-title":"Food Front"},{"issue":"2","key":"R26-20260728","doi-asserted-by":"crossref","first-page":"95","DOI":"10.14499\/indonesianjcanchemoprev10iss2pp95-100","article-title":"Selectivity index of Alpinia galanga extract and 1\u2019-acetoxychavicol acetate on cancer cell lines","volume":"10","author":"Da\u2019i","year":"2019","journal-title":"Indonesia J Cancer Chemoprevent"},{"key":"R27-20260728","doi-asserted-by":"crossref","first-page":"217","DOI":"10.2147\/JEP.S405433","article-title":"Anthocyanin-containing purple sweet potato (Ipomoea batatas L.) synbiotic yogurt inhibited 3T3-L1 adipogenesis by suppressing white adipocyte-specific genes","volume":"15","author":"Ariyanto","year":"2023","journal-title":"J Exp Pharmacol"},{"key":"R28-20260728","doi-asserted-by":"crossref","first-page":"S207","DOI":"10.56499\/jppres24.2292_13.s1.207","article-title":"Phytochemical profiling and tyrosinase inhibitory activity of Illicium verum Hook f. in vitro and in silico insights","volume":"13","author":"Rahman","year":"2025","journal-title":"J Pharm Pharm Res"},{"issue":"2","key":"R29-20260728","doi-asserted-by":"crossref","first-page":"88","DOI":"10.20884\/1.jm.2020.15.2.579","article-title":"Reverse docking, molecular docking, absorption, distribution, and toxicity prediction of artemisinin as an anti-diabetic candidate","volume":"15","author":"Ruswanto","year":"2020","journal-title":"Molekul"},{"key":"R31-20260728","doi-asserted-by":"crossref","first-page":"108090","DOI":"10.1016\/j.bioorg.2024.108090","article-title":"Synthesis, in vivo evaluation, and in silico molecular docking of benzo[h]quinoline derivatives as potential Culex pipiens L. larvicides","volume":"154","author":"Ramadan,","year":"2025","journal-title":"Bioorg Chem"},{"issue":"1","key":"R32-20260728","doi-asserted-by":"crossref","first-page":"54","DOI":"10.22146\/ijbiotech.62194","article-title":"Introducing a two-dimensional graph of docking score difference vs. similarity of ligand-receptor interactions","volume":"26","author":"Pratama","year":"2021","journal-title":"Indonesia J Biotechnol"},{"issue":"8","key":"R33-20260728","doi-asserted-by":"crossref","first-page":"3696","DOI":"10.1021\/acs.jctc.5b00255","article-title":"ff14SB: Improving the accuracy of protein side chain and backbone parameters from ff99SB","volume":"11","author":"Maier","year":"2015","journal-title":"J Chem Theory Comput"},{"issue":"9","key":"R34-20260728","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1002\/jcc.20035","article-title":"Development and testing of a general amber force field","volume":"25","author":"Wang","year":"2004","journal-title":"J Comput Chem"},{"issue":"1","key":"R35-20260728","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/s42004-024-01114-5","article-title":"Convergence and equilibrium in molecular dynamics simulations","volume":"7","author":"Ormeno","year":"2024","journal-title":"Commun Chem"},{"key":"R36-20260728","doi-asserted-by":"crossref","first-page":"173521","DOI":"10.1155\/2012\/173521","article-title":"Relaxation estimation of RMSD in molecular dynamics immunosimulations","volume":"2012","author":"Schreiner","year":"2012","journal-title":"Comput Math Methods Med"},{"issue":"9","key":"R37-20260728","doi-asserted-by":"crossref","first-page":"e10694","DOI":"10.1016\/j.heliyon.2022.e10694","article-title":"Design, molecular docking, and molecular dynamics of thiourea-iron (III) metal complexes as NUDT5 inhibitors for breast cancer treatment","volume":"8","author":"Ruswanto","year":"2022","journal-title":"Heliyon"},{"issue":"2","key":"R38-20260728","doi-asserted-by":"crossref","first-page":"239","DOI":"10.23960\/jtaf.v6i2.1849","article-title":"Molecular dynamics analysis of egg white lysozyme using the Lennard-Jones potential model in GROMACS","volume":"6","author":"Prayoga","year":"2018","journal-title":"J Teori Apl Fisika"},{"issue":"1","key":"R39-20260728","doi-asserted-by":"crossref","first-page":"89","DOI":"10.15408\/jkv.v9i1.31481","article-title":"The potency of alkaloid derivatives as anti-breast cancer candidates: in silico study","volume":"9","author":"Renadi","year":"2023","journal-title":"J Kimia Valensi"},{"issue":"6","key":"R40-20260728","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.pharma.2012.09.005","article-title":"Interest of designed cyclodextrin tools in gene delivery","volume":"70","author":"Duval","year":"2012","journal-title":"Ann Pharm Fr"},{"key":"R41-20260728","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.ab.2016.06.025","article-title":"Determination of half-maximal inhibitory concentration using biosensor-based protein interaction analysis","volume":"508","author":"Aykul","year":"2016","journal-title":"Anal Biochem,"},{"key":"R42-20260728","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0065-2571(84)90007-4","article-title":"Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors","volume":"22","author":"Chou","year":"1984","journal-title":"Adv Enzyme Regul"},{"issue":"3","key":"R43-20260728","doi-asserted-by":"crossref","first-page":"531","DOI":"10.3390\/biomedicines10030531","article-title":"Diosmetin exerts synergistic effects in combination with 5-fluorouracil in colorectal cancer cells","volume":"10","author":"Kamran","year":"2022","journal-title":"Biomedicines"},{"issue":"3","key":"R44-20260728","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1097\/MS9.0000000000002922","article-title":"Synergistic effects of doxorubicin and coumarin on colorectal cancer cell proliferation and EMT modulation: in silico and in vitro study","volume":"87","author":"Khakparaghi","year":"2025","journal-title":"Ann Med Surg (Lond)"},{"issue":"7","key":"R45-20260728","doi-asserted-by":"crossref","first-page":"11808","DOI":"10.3390\/molecules200711808","article-title":"The anticancer, antioxidant and antimicrobial properties of the sesquiterpene \u03b2-caryophyllene from the essential oil of Aquilaria crassna","volume":"20","author":"Dahham","year":"2015","journal-title":"Molecules"},{"issue":"2","key":"R46-20260728","doi-asserted-by":"crossref","DOI":"10.1039\/D0MD00317D","article-title":"Normal breast epithelial MCF-10A cells to evaluate the safety of carbon dots","volume":"12","author":"Vale","year":"2020","journal-title":"RSC Med Chem"}],"container-title":["Research in Pharmaceutical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.4103\/RPS.RPS_108_25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T04:02:56Z","timestamp":1785211376000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.4103\/RPS.RPS_108_25"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":43,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.4103\/rps.rps_108_25","relation":{},"ISSN":["1735-5362","1735-9414"],"issn-type":[{"value":"1735-5362","type":"print"},{"value":"1735-9414","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2025-06-26","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-06","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}