{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T20:00:39Z","timestamp":1774987239852,"version":"3.50.1"},"reference-count":63,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The All-India Council for Technical Education Research Promotion Scheme","award":["No-8-200\/RIFD\/RPS(POLICY-1)"],"award-info":[{"award-number":["No-8-200\/RIFD\/RPS(POLICY-1)"]}]},{"name":"The All-India Council for Technical Education Research Promotion Scheme","award":["REG\/DIR(R)\/URG\/54\/2011-12\/5293"],"award-info":[{"award-number":["REG\/DIR(R)\/URG\/54\/2011-12\/5293"]}]},{"name":"JSS Academy of Higher Education and Research (Mysore, Karnataka)","award":["No-8-200\/RIFD\/RPS(POLICY-1)"],"award-info":[{"award-number":["No-8-200\/RIFD\/RPS(POLICY-1)"]}]},{"name":"JSS Academy of Higher Education and Research (Mysore, Karnataka)","award":["REG\/DIR(R)\/URG\/54\/2011-12\/5293"],"award-info":[{"award-number":["REG\/DIR(R)\/URG\/54\/2011-12\/5293"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Breast Cancer Gene 1 (BRCA1) offers a potential approach for ER\u03b1 repression by blocking cyclin D1\u2019s interaction with ER\u03b1, which prevents cells from growing and dividing too rapidly or uncontrollably. When BRCA1 levels are low, BRCA1 mimetics fit into the BRCA1-binding pocket within ER\u03b1, mimicking the ability of BRCA1 to inhibit ER\u03b1 activity. This study aims to identify a novel class of lead molecules for BRCA1 mimetics for ER-positive breast cancer, distinct from conventional antiestrogen therapies in their mechanism of action. In this article, coumarin thiosemicarbazone hybrids were synthesized from 7-hydroxy 4-methyl coumarin\/4-hydroxy coumarin and thiosemicarbazide with different aldehydes and evaluated for their ER\u03b1 repression activity. The most active compounds in the series, 9b, 9l, and 9m, exhibited significant potency with an IC50 value of 14.49 \u00b5M, 35.08 \u00b5M and 42.12 \u00b5M, respectively, compared to raloxifene (reported) as the positive control with an IC50 value of 13.7 \u00b5M. The gene expression study confirmed the downregulation of the cyclin D1 gene for the compounds 9l (\u22120.217) and 9m (\u22120.214). Similarly, the downregulation of the BCL2 gene for the compounds 9b (\u22120.373), 9l (\u22120.320), and 9m (\u22120.376). Also, molecular docking studies and MMGBSA were performed to determine key interactions between compounds and ER\u03b1 at the BRCA1 binding pocket (AA 338\u2013387). In silico, ADMET properties were executed to illustrate the druggability and safety of the novel derivatives. In silico, in vitro, and gene expression studies revealed that among all the compounds, 9b, 9l, and 9m are promising candidates for the development of lead molecules targeting ER\u03b1 inhibitors for breast cancer treatment. Moreover, the concept of ER\u03b1 repression with small molecules as BRCA1 mimetics is novel. In general, it can be concluded that these compounds can serve as promising leads to the design of potential BRCA1 mimetics.<\/jats:p>","DOI":"10.3390\/life15040581","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T07:47:44Z","timestamp":1743580064000},"page":"581","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A New Class of BRCA1 Mimetics for ER\u03b1-Positive Breast Cancer Therapy: Design, Synthesis, In Silico Screening, In Vitro Assay, and Gene Expression Analysis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5333-1098","authenticated-orcid":false,"given":"Pottabathula","family":"Shyam Sundar","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Vasantidevi Patil Institute of Pharmacy, Kodoli 416114, Maharastra, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4633-6621","authenticated-orcid":false,"given":"Jubie","family":"Selvaraj","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty 643001, Tamilnadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0165-7912","authenticated-orcid":false,"given":"Veerachamy","family":"Alagarsamy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, MNR College of Pharmacy, Sangareddy 502294, Telangana, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9863-4452","authenticated-orcid":false,"given":"Viswas Raja","family":"Solomon","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, MNR College of Pharmacy, Sangareddy 502294, Telangana, India"},{"name":"Department of Chemistry, University of Saskatchewan, Saskatoon, SK S7N 5A2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jawahar","family":"Natarajan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty 643001, Tamilnadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.1002\/cncr.32887","article-title":"Breast Cancer Early Detection: A Phased Approach to Implementation","volume":"126","author":"Ginsburg","year":"2020","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA","volume":"71","author":"Sung","year":"2021","journal-title":"Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1002\/cncr.32910","article-title":"Breast Cancer Treatment: A Phased Approach to Implementation","volume":"126","author":"Mutebi","year":"2020","journal-title":"Cancer"},{"key":"ref_4","unstructured":"(2024, August 14). WHO Launches New Roadmap on Breast Cancer. Available online: https:\/\/www.who.int\/news\/item\/03-02-2023-who-launches-new-roadmap-on-breast-cancer."},{"key":"ref_5","unstructured":"(2024, August 14). BRCA: The Breast Cancer Gene-BRCA Mutations & Risks. Available online: https:\/\/www.nationalbreastcancer.org\/what-is-brca\/."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1038\/ncb1171","article-title":"Identification of BRCA1-IRIS, a BRCA1 Locus Product","volume":"6","author":"ElShamy","year":"2004","journal-title":"Nat. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/6029","article-title":"Localization of Human BRCA1 and Its Loss in High-Grade, Non-Inherited Breast Carcinomas","volume":"21","author":"Wilson","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1073\/pnas.89.1.246","article-title":"Determination of Ligand-Binding Specificity by Alternative Splicing: Two Distinct Growth Factor Receptors Encoded by a Single Gene","volume":"89","author":"Miki","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1056\/NEJM199705153362001","article-title":"The Risk of Cancer Associated with Specific Mutations of BRCA1 and BRCA2 among Ashkenazi Jews","volume":"336","author":"Struewing","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1093\/nar\/gkl010","article-title":"BRCA1: Cell Cycle Checkpoint, Genetic Instability, DNA Damage Response and Cancer Evolution","volume":"34","author":"Deng","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1158\/1535-7163.MCT-05-0471","article-title":"BRCA1 at the Crossroad of Multiple Cellular Pathways: Approaches for Therapeutic Interventions","volume":"5","author":"Yarden","year":"2006","journal-title":"Mol. Cancer Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s10555-012-9403-7","article-title":"Mouse Models of BRCA1 and Their Application to Breast Cancer Research","volume":"32","author":"Dine","year":"2013","journal-title":"Cancer Metastasis Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1007\/s12015-012-9354-y","article-title":"BRCA1-Conductor of the Breast Stem Cell Orchestra: The Role of BRCA1 in Mammary Gland Development and Identification of Cell of Origin of BRCA1 Mutant Breast Cancer","volume":"8","author":"Buckley","year":"2012","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"R113","DOI":"10.1093\/hmg\/ddg082","article-title":"Roles of BRCA1 in DNA Damage Repair: A Link between Development and Cancer","volume":"12","author":"Deng","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1101\/gad.1050003","article-title":"Senescence, Aging, and Malignant Transformation Mediated by P53 in Mice Lacking the Brca1 Full-Length Isoform","volume":"17","author":"Cao","year":"2003","journal-title":"Genes Dev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6557","DOI":"10.1158\/0008-5472.CAN-05-0486","article-title":"Cyclin D1 Antagonizes BRCA1 Repression of Estrogen Receptor \u03b1 Activity","volume":"65","author":"Wang","year":"2005","journal-title":"Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/sj.onc.1204073","article-title":"Role of Direct Interaction in BRCA1 Inhibition of Estrogen Receptor Activity","volume":"20","author":"Fan","year":"2001","journal-title":"Oncogene"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1038\/sj.onc.1208190","article-title":"Structural Determinants of the BRCA1: Estrogen Receptor Interaction","volume":"24","author":"Ma","year":"2005","journal-title":"Oncogene"},{"key":"ref_19","first-page":"792","article-title":"Dual Modulators of P53 and Cyclin D in ER Alpha Signaling by Albumin Nanovectors Bearing Zinc Chaperones for ER-Positive Breast Cancer Therapy","volume":"21","author":"Sundar","year":"2020","journal-title":"Mini-Rev. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.bioorg.2017.02.011","article-title":"Estrogen Receptor Agonists\/Antagonists in Breast Cancer Therapy: A Critical Review","volume":"71","author":"Jubie","year":"2017","journal-title":"Bioorg. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"786","DOI":"10.2174\/1573409916666191231102046","article-title":"A New Class of Coumate Benzimidazole Hybrids as BRCA 1 Mimetics Through Unconventional Binding Mode; Synthesis and Preliminary Cytotoxicity Screening","volume":"16","author":"Jubie","year":"2019","journal-title":"Curr. Comput. Aided. Drug Des."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3484","DOI":"10.22270\/jmpas.V10I4.1383","article-title":"Potential Coumarin Thiosemicarbazone Hybrids as BRCA-1 Mimetics for ER Positive Breast Cancer Therapy: An In-Silico Approach","volume":"10","author":"Naresh","year":"2021","journal-title":"J. Med. Pharm. Allied Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.ejmech.2015.07.028","article-title":"Thiosemicarbazone Modification of 3-Acetyl Coumarin Inhibits A\u03b2 Peptide Aggregation and Protect against A\u03b2-Induced Cytotoxicity","volume":"121","author":"Ranade","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4309","DOI":"10.1128\/MCB.22.12.4309-4318.2002","article-title":"The RASSF1A Tumor Suppressor Blocks Cell Cycle Progression and Inhibits Cyclin D1 Accumulation","volume":"22","author":"Shivakumar","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1093\/emboj\/18.5.1367","article-title":"Transcriptional Regulation of the Cyclin D1 Promoter by STAT5: Its Involvement in Cytokine-dependent Growth of Hematopoietic Cells","volume":"18","author":"Matsumura","year":"1999","journal-title":"EMBO J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/369669a0","article-title":"Mammary Hyperplasia and Carcinoma in MMTV-Cyclin D1 Transgenic Mice","volume":"369","author":"Wang","year":"1994","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s13148-010-0018-y","article-title":"The Elements of Human Cyclin D1 Promoter and Regulation Involved","volume":"2","author":"Guo","year":"2011","journal-title":"Clin. Epigenetics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4499","DOI":"10.1128\/MCB.18.8.4499","article-title":"C-Myc or Cyclin D1 Mimics Estrogen Effects on Cyclin E-Cdk2 Activation and Cell Cycle Reentry","volume":"18","author":"Prall","year":"1998","journal-title":"Mol. Cell. Biol."},{"key":"ref_29","unstructured":"(2024, December 02). Inducible Overexpression of Cyclin D1 in Breast Cancer Cells Reverses the Growth-Inhibitory Effects of Antiestrogens.|Clinical Cancer Research|American Association for Cancer Research. Available online: https:\/\/aacrjournals.org\/clincancerres\/article\/3\/6\/849\/7941\/Inducible-overexpression-of-cyclin-D1-in-breast."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.jviromet.2005.03.001","article-title":"Real-Time PCR Quantitation of Hepatitis B Virus DNA Using Automated Sample Preparation and Murine Cytomegalovirus Internal Control","volume":"126","author":"Garson","year":"2005","journal-title":"J. Virol. Methods"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/S0301-472X(02)00806-8","article-title":"Gene Quantification Using Real-Time Quantitative PCR: An Emerging Technology Hits the Mainstream","volume":"30","author":"Ginzinger","year":"2002","journal-title":"Exp. Hematol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"75","DOI":"10.2144\/05391RV01","article-title":"Real-Time PCR for MRNA Quantitation","volume":"39","author":"Wong","year":"2018","journal-title":"Biotechniques"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1677\/jme.0.0250169","article-title":"Absolute Quantification of MRNA Using Real-Time Reverse Transcription Polymerase Chain Reaction Assays","volume":"25","author":"Bustin","year":"2000","journal-title":"J. Mol. Endocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1023\/B:BILE.0000019559.84305.47","article-title":"Determination of Stable Housekeeping Genes, Differentially Regulated Target Genes and Sample Integrity: BestKeeper\u2013Excel-Based Tool Using Pair-Wise Correlations","volume":"26","author":"Pfaffl","year":"2004","journal-title":"Biotechnol. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Vandesompele, J., De Preter, K., Pattyn, F., Poppe, B., Van Roy, N., De Paepe, A., and Speleman, F. (2002). Accurate Normalization of Real-Time Quantitative RT-PCR Data by Geometric Averaging of Multiple Internal Control Genes. Genome Biol., 3.","DOI":"10.1186\/gb-2002-3-7-research0034"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Bao, Z., Huang, Y., Chen, J., Wang, Z., Qian, J., Xu, J., and Zhao, Y. (2019). Validation of Reference Genes for Gene Expression Normalization in RAW264.7 Cells under Different Conditions. BioMed Res. Int., 2019.","DOI":"10.1155\/2019\/6131879"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1016\/j.bbrc.2003.11.177","article-title":"Guideline to Reference Gene Selection for Quantitative Real-Time PCR","volume":"313","author":"Thulke","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_38","unstructured":"Rao, X., Huang, X., Zhou, Z., and Lin, X. (2013). An Improvement of the 2\u02c6(\u2013Delta Delta CT) Method for Quantitative Real-Time Polymerase Chain Reaction Data Analysis. Biostat. Bioinforma. Biomath., 3."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1093\/nar\/gkj109","article-title":"Biogrid: A General Repository for Interaction Datasets","volume":"34","author":"Stark","year":"2006","journal-title":"Nucleic Acids. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7730","DOI":"10.1038\/sj.onc.1205971","article-title":"Direct Interaction between BRCA1 and the Estrogen Receptor Regulates Vascular Endothelial Growth Factor (VEGF) Transcription and Secretion in Breast Cancer Cells","volume":"21","author":"Kawai","year":"2002","journal-title":"Oncogene"},{"key":"ref_41","first-page":"141","article-title":"P300 Modulates the BRCA1 Inhibition of Estrogen Receptor Activity","volume":"62","author":"Fan","year":"2002","journal-title":"Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1016\/j.biocel.2005.12.017","article-title":"Geminin Is Bound to Chromatin in G2\/M Phase to Promote Proper Cytokinesis","volume":"38","author":"Nakuci","year":"2006","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"31257","DOI":"10.1074\/jbc.M502577200","article-title":"Mechanism of the Maturation Process of SARS-CoV 3CL Protease","volume":"280","author":"Hsu","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.biocel.2009.12.025","article-title":"Negative Feedback Loop of BRCA1-BARD1 Ubiquitin Ligase on Estrogen Receptor Alpha Stability and Activity Antagonized by Cancer-Associated Isoform of BARD1","volume":"42","author":"Dizin","year":"2010","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1210\/me.2009-0218","article-title":"BRCA1 Regulates Acetylation and Ubiquitination of Estrogen Receptor-Alpha","volume":"24","author":"Ma","year":"2010","journal-title":"Mol. Endocrinol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1210\/me.2006-0397","article-title":"Growth Factor Signaling Pathways Modulate BRCA1 Repression of Estrogen Receptor-Alpha Activity","volume":"21","author":"Ma","year":"2007","journal-title":"Mol. Endocrinol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1016\/j.neo.2014.09.013","article-title":"Elevated Estrogen Receptor-\u03b1 in VHL-Deficient Condition Induces Microtubule Organizing Center Amplification via Disruption of BRCA1\/Rad51 Interaction","volume":"16","author":"Jung","year":"2014","journal-title":"Neoplasia"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1002\/pro.3091","article-title":"Tuning BRCA1 and BARD1 Activity to Investigate RING Ubiquitin Ligase Mechanisms","volume":"26","author":"Stewart","year":"2017","journal-title":"Protein Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"9587","DOI":"10.1073\/pnas.171174298","article-title":"BRCA1 Mediates Ligand-Independent Transcriptional Repression of the Estrogen Receptor","volume":"98","author":"Zheng","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/0022-1759(86)90215-2","article-title":"Use of MTT Colorimetric Assay to Measure Cell Activation","volume":"94","author":"Gerlier","year":"1986","journal-title":"J. Immunol. Methods"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1006\/abbi.1993.1311","article-title":"Characterization of the Cellular Reduction of 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT): Subcellular Localization, Substrate Dependence, and Involvement of Mitochondrial Electron Transport in MTT Reduction","volume":"303","author":"Berridge","year":"1993","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Singh, M., Patra, S., and Singh, R.K. (2021). Common Techniques and Methods for Screening of Natural Products for Developing of Anticancer Drugs. Evolutionary Diversity as a Source for Anticancer Molecules, Academic Press.","DOI":"10.1016\/B978-0-12-821710-8.00015-1"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"D362","DOI":"10.1093\/nar\/gkw937","article-title":"The STRING Database in 2017: Quality-Controlled Protein-Protein Association Networks, Made Broadly Accessible","volume":"45","author":"Szklarczyk","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"D447","DOI":"10.1093\/nar\/gku1003","article-title":"STRING V10: Protein-Protein Interaction Networks, Integrated over the Tree of Life","volume":"43","author":"Szklarczyk","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"8155","DOI":"10.7314\/APJCP.2014.15.19.8155","article-title":"In Silico Docking Studies of Selected Flavonoids-Natural Healing Agents Against Breast Cancer","volume":"15","author":"Suganya","year":"2014","journal-title":"Asian Pacific J. Cancer Prev."},{"key":"ref_56","first-page":"e1298","article-title":"Hengphasatporn Using PyMOL as a Platform for Computational Drug Design","volume":"9","author":"Nutho","year":"2020","journal-title":"Science"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3714","DOI":"10.1021\/jm000942e","article-title":"Fast Calculation of Molecular Polar Surface Area as a Sum of Fragment-Based Contributions and Its Application to the Prediction of Drug Transport Properties","volume":"43","author":"Ertl","year":"2000","journal-title":"J. Med. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3284","DOI":"10.1021\/ci500467k","article-title":"ILOGP: A Simple, Robust, and Efficient Description of n-Octanol\/Water Partition Coefficient for Drug Design Using the GB\/SA Approach","volume":"54","author":"Daina","year":"2014","journal-title":"J. Chem. Inf. Model."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(96)00423-1","article-title":"Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Discovery and Development Settings","volume":"23","author":"Lipinski","year":"1997","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1021\/ci200387c","article-title":"Revisiting the General Solubility Equation: In Silico Prediction of Aqueous Solubility Incorporating the Effect of Topographical Polar Surface Area","volume":"52","author":"Ali","year":"2012","journal-title":"J. Chem. Inf. Model."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1002\/cmdc.201600182","article-title":"A BOILED-Egg to Predict Gastrointestinal Absorption and Brain Penetration of Small Molecules","volume":"11","author":"Daina","year":"2016","journal-title":"ChemMedChem"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"85","DOI":"10.5487\/TR.2011.27.2.085","article-title":"The Effect of Selective Estrogen Receptor Modulators (Serms) on the Tamoxifen Resistant Breast Cancer Cells","volume":"27","author":"Chang","year":"2011","journal-title":"Toxicol. Res."},{"key":"ref_63","unstructured":"(2022, December 24). PyMOL|Pymol.Org. Available online: https:\/\/pymol.org\/2\/."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/4\/581\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:08:01Z","timestamp":1760029681000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/4\/581"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,1]]},"references-count":63,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["life15040581"],"URL":"https:\/\/doi.org\/10.3390\/life15040581","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,1]]}}}