{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,8]],"date-time":"2026-11-08T02:25:26Z","timestamp":1794104726579,"version":"4.8.0"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T00:00:00Z","timestamp":1695600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Breast and lung cancer are two of the most lethal forms of cancer, responsible for a disproportionately high number of deaths worldwide. Both doctors and cancer patients express alarm about the rising incidence of the disease globally. Although targeted treatment has achieved enormous advancements, it is not without its drawbacks. Numerous medicines and chemotherapeutic drugs have been authorized by the FDA; nevertheless, they can be quite costly and often fall short of completely curing the condition. Therefore, this investigation has been conducted to identify a potential medication against breast and lung cancer through structural modification of genistein. Genistein is the active compound in <jats:italic>Glycyrrhiza glabra<\/jats:italic> (licorice), and it exhibits solid anticancer efficiency against various cancers, including breast cancer, lung cancer, and brain cancer. Hence, the design of its analogs with the interchange of five functional groups\u2014COOH, NH<jats:sub>2<\/jats:sub> and OCH<jats:sub>3<\/jats:sub>, Benzene, and NH-CH<jats:sub>2<\/jats:sub>-CH<jats:sub>2<\/jats:sub>-OH\u2014have been employed to enhance affinities compared to primary genistein. Additionally, advanced computational studies such as PASS prediction, molecular docking, ADMET, and molecular dynamics simulation were conducted. Firstly, the PASS prediction spectrum was analyzed, revealing that the designed genistein analogs exhibit improved antineoplastic activity. In the prediction data, breast and lung cancer were selected as primary targets. Subsequently, other computational investigations were gradually conducted. The mentioned compounds have shown acceptable results for <jats:italic>in silico<\/jats:italic> ADME, AMES toxicity, and hepatotoxicity estimations, which are fundamental for their oral medication. It is noteworthy that the initial binding affinity was only \u22128.7 kcal\/mol against the breast cancer targeted protein (PDB ID: 3HB5). However, after the modification of the functional group, when calculating the binding affinities, it becomes apparent that the binding affinities increase gradually, reaching a maximum of \u221211.0 and \u221210.0 kcal\/mol. Similarly, the initial binding affinity was only \u22128.0 kcal\/mol against lung cancer (PDB ID: 2P85), but after the addition of binding affinity, it reached \u22129.5 kcal\/mol. Finally, a molecular dynamics simulation was conducted to study the molecular models over 100 ns and examine the stability of the docked complexes. The results indicate that the selected complexes remain highly stable throughout the 100-ns molecular dynamics simulation runs, displaying strong correlations with the binding of targeted ligands within the active site of the selected protein. It is important to further investigate and proceed to clinical or wet lab experiments to determine the practical value of the proposed compounds.<\/jats:p>","DOI":"10.3389\/fonc.2023.1228865","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T08:12:19Z","timestamp":1695715939000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":36,"title":["Revolutionizing anti-cancer drug discovery against breast cancer and lung cancer by modification of natural genistein: an advanced computational and drug design approach"],"prefix":"10.3389","volume":"13","author":[{"given":"Shopnil","family":"Akash","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shabana","family":"Bibi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Partha","family":"Biswas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobendu","family":"Mukerjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhrubo Ahmed","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Nazmul","family":"Hasan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazneen Ahmeda","family":"Sultana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Eram","family":"Hosen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousef A. Bin","family":"Jardan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiba-Allah","family":"Nafidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Bourhia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1126\/science.123.3191.309","article-title":"On the origin of cancer cells","volume":"123","author":"Warburg","year":"1956","journal-title":"Science"},{"key":"B2","doi-asserted-by":"crossref","DOI":"10.1109\/ICSIPA.2017.8120587","article-title":"Classification of benign and Malignant tumors in histopathology images","author":"Samah","year":"2017"},{"key":"B3","volume-title":"Introduction to the cellular and molecular biology of cancer","author":"Franks","year":"1997"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/BF00173886","article-title":"Modelling the growth of solid tumours and incorporating a method for their classification using nonlinear elasticity theory","volume":"31","author":"Chaplain","year":"1993","journal-title":"J Math Biol"},{"key":"B5","article-title":"Differentiation of Malignant to benign cells","volume":"31","author":"Pierce","year":"1971","journal-title":"Cancer Res"},{"key":"B6","article-title":"Differential expression of the epidermal growth factor receptor and its ligands in primary non-small cell lung cancers and adjacent benign lung","volume":"53","author":"Rusch","year":"1993","journal-title":"Cancer Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3762\/bjnano.5.52","article-title":"The softening of human bladder cancer cells happens at an early stage of the Malignancy process","volume":"5","author":"Ramos","year":"2014","journal-title":"Beilstein J nanotechnol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/boc.201600078","article-title":"Are cancer cells really softer than normal cells","volume":"109","author":"Alibert","year":"2017","journal-title":"Biol Cell"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19850215)55:4<805::AID-CNCR2820550419>3.0.CO;2-Z","article-title":"Papillary carcinoma of the thyroid. A clinicopathologic study of 241 cases treated at the University of Florence, Italy","volume":"55","author":"Carcangiu","year":"1985","journal-title":"Cancer"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1965","DOI":"10.1007\/s11538-019-00597-x","article-title":"A mathematical framework for modelling the metastatic spread of cancer","volume":"81","author":"Franssen","year":"2019","journal-title":"Bull Math Biol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1146\/annurev.pu.17.050196.000403","article-title":"Epidemiology and prevention of breast cancer","volume":"17","author":"Kelsey","year":"1996","journal-title":"Annu Rev Public Health"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.7314\/APJCP.2016.17.S3.43","article-title":"Incidence and mortality and epidemiology of breast cancer in the world","volume":"17","author":"Ghoncheh","year":"2016","journal-title":"Asian Pacific J Cancer Prev"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20978","article-title":"Breast cancer in sub-Saharan Africa: how does it relate to breast cancer in African-American women","volume":"103","author":"Fregene","year":"2005","journal-title":"Cancer: Interdiscip Int J Am Cancer Soc"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a117079","article-title":"Reproductive risk factors in a prospective study of breast cancer: the Nurses\u2019 Health Study","volume":"139","author":"Rosner","year":"1994","journal-title":"Am J Epidemiol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1097\/SPC.0000000000000184","article-title":"Sexual identity after breast cancer: sexuality, body image, and relationship repercussions","volume":"10","author":"Male","year":"2016","journal-title":"Curr Opin Support Palliat Care"},{"key":"B16","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1002\/pon.744","article-title":"Psychosocial problems among younger women with breast cancer","volume":"13","author":"Avis","year":"2004","journal-title":"Psycho-Oncol: J Psychological Soc Behav Dimensions Cancer"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.945102","article-title":"The current treatments for non-small cell lung cancer","author":"Guo","year":"2022","journal-title":"Front Oncol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2112431","article-title":"Trastuzumab deruxtecan in HER2-mutant non\u2013small-cell lung cancer","volume":"386","author":"Li","year":"2022","journal-title":"N Engl J Med"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12859-021-04376-1","article-title":"Non-small-cell lung cancer classification","volume":"22","author":"Carrillo-Perez","year":"2021","journal-title":"RNA-Seq Histol Imaging probability fusion. BMC Bioinf"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12816","article-title":"Metabolic enzyme ACSL3 is a prognostic biomarker and correlates with anticancer effectiveness of statins in non-small cell lung cancer","volume":"14","author":"Fern\u00e1ndez","year":"2020","journal-title":"Mol Oncol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"48","DOI":"10.3390\/life12010048","article-title":"Comparison of anticancer drug toxicities: paradigm shift in adverse effect profile","volume":"12","author":"Basak","year":"2021","journal-title":"Life"},{"key":"B22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-030-04408-4_1","article-title":"Phytochemical constituents and pharmacological effects of licorice: a review","volume-title":"Plant and human health, Volume 3: Pharmacology and therapeutic uses","author":"Mamedov","year":"2019"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3945\/an.114.008052","article-title":"Genistein and cancer: current status, challenges, and future directions","volume":"6","author":"Spagnuolo","year":"2015","journal-title":"Adv Nutr"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e14228","DOI":"10.1111\/jfbc.14228","article-title":"Therapeutic potentials of genistein: New insights and perspectives","volume":"46","author":"Rasheed","year":"2022","journal-title":"J Food Biochem"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.36349\/easjpp.2019.v01i05.004","article-title":"In-silico analysis to access the antibacterial effect of genistein: molecular docking approach","volume":"1","author":"Kumar","year":"2019","journal-title":"EAS J Pharm Pharmacol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2008.03.052","article-title":"Multi-targeted therapy of cancer by genistein","volume":"269","author":"Banerjee","year":"2008","journal-title":"Cancer Lett"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.820969","article-title":"Genistein: a review on its anti-inflammatory properties","volume":"13","author":"Goh","year":"2022","journal-title":"Front Pharmacol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/j.foodchem.2015.09.085","article-title":"Understanding genistein in cancer: The \u201cgood\u201d and the \u201cbad\u201d effects: A review","volume":"196","author":"Russo","year":"2016","journal-title":"Food Chem"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3390\/cimb43030106","article-title":"Genistein: a potent anti-breast cancer agent","volume":"43","author":"Bhat","year":"2021","journal-title":"Curr Issues Mol Biol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.nutres.2019.03.015","article-title":"Individual factors define the overall effects of dietary genistein exposure on breast cancer patients","volume":"67","author":"Liu","year":"2019","journal-title":"Nutr Res"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/68.6.1400S","article-title":"Genistein studies in rats: potential for breast cancer prevention and reproductive and developmental toxicity","volume":"68","author":"Lamartiniere","year":"1998","journal-title":"Am J Clin Nutr"},{"key":"B32","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1007\/s42250-020-00162-3","article-title":"In-silico molecular docking and ADME\/pharmacokinetic prediction studies of some novel carboxamide derivatives as anti-tubercular agents","volume":"3","author":"Abdullahi","year":"2020","journal-title":"Chem Afr"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10719-021-10039-3","article-title":"Methyl \u03b2-D-galactopyranoside esters as potential inhibitors for SARS-CoV-2 protease enzyme: synthesis, antimicrobial, PASS, molecular docking, molecular dynamics simulations and quantum computations","author":"Amin","year":"2021","journal-title":"Glycoconjugate J"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1021\/ci020048r","article-title":"PASS biological activity spectrum predictions in the enhanced open NCI database browser","volume":"43","author":"Poroikov","year":"2003","journal-title":"J Chem Inf Comput Sci"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.35812\/CelluloseChemTechnol.2021.55.44","article-title":"Monosaccharide derivatives: synthesis, antimicrobial, pass, antiviral and molecular docking studies against SARS-COV-2 Mpro inhibitors","volume":"55","author":"Yasmin","year":"2021","journal-title":"J Cellulose Chem Technol"},{"key":"B36","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/978-981-19-3092-8_15","article-title":"Introduction to Materials Studio Software for the Atomistic-Scale Simulations","volume-title":"Forcefields for Atomistic-Scale Simulations: Materials and Applications","author":"Shankar","year":"2022"},{"key":"B37","doi-asserted-by":"publisher","first-page":"bbaa160","DOI":"10.1093\/bib\/bbaa160","article-title":"Current development of integrated web servers for preclinical safety and pharmacokinetics assessments in drug development","volume":"22","author":"Hsiao","year":"2021","journal-title":"Briefings Bioinf"},{"key":"B38","article-title":"Pharmacoinformatics based in silico Molecular Dynamics Simulation for Screening Phytochemicals as AMPK and INSR Modulators for Polycystic Ovarian Syndrome from Medicinal Plants","author":"Pachiappan","year":""},{"key":"B39","doi-asserted-by":"publisher","first-page":"14","DOI":"10.31643\/2023\/6445.13","article-title":"SwissADME and pkCSM webservers predictors: An integrated online platform for accurate and comprehensive predictions for in silico ADME\/T properties of artemisinin and its derivatives","volume":"325","author":"Azzam","year":"2023","journal-title":"Kompleksnoe Ispolzovanie Mineralnogo Syra= Complex Use mineral Resour"},{"key":"B40","article-title":"Binary and ternary crystal structure analyses of a novel inhibitor with 17\u03b2-HSD type 1: a lead compound for breast cancer therapy","volume":"424","author":"Mazumdar","year":"2009","journal-title":"J.B.J"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702361200","article-title":"Structure of the human lung cytochrome P450 2A13","volume":"282","author":"Smith","year":"2007","journal-title":"J Biol Chem"},{"key":"B42","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.heliyon.2021.e07509","article-title":"The effect of alkyl chain and electronegative atoms in anion on biological activity of anilinium carboxylate bioactive ionic liquids and computational approaches by DFT functional and molecular docking","author":"Kumer","year":"2021","journal-title":"Heliyon"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.proche.2014.12.007","article-title":"Molecular Docking studies of chemical constituents of Tinospora cordifolia on glycogen phosphorylase","volume":"13","author":"Herowati","year":"2014","journal-title":"Proc Chem"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.2c00995","article-title":"Qualitative estimation of protein\u2013ligand complex stability through thermal titration molecular dynamics simulations","volume":"62","author":"Pavan","year":"2022","journal-title":"J Chem Inf Model"},{"key":"B45","volume-title":"Molecular simulations of protein-induced membrane remodeling","author":"Bradley","year":"2016"},{"key":"B46","first-page":"84","article-title":"Scalable algorithms for molecular dynamics simulations on commodity clusters","author":"Bowers","year":"2006"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmgm.2019.08.012","article-title":"Molecular docking and dynamic approach to virtual screen inhibitors against Esbp of Candidatus Liberibacter asiaticus","volume":"92","author":"Saini","year":"2019","journal-title":"J Mol Graphics Model"},{"key":"B48","doi-asserted-by":"publisher","first-page":"103414","DOI":"10.1016\/j.compbiomed.2019.103414","article-title":"Pharmacoinformatics-based identification of potential bioactive compounds against Ebola virus protein VP24","volume":"113","author":"Kwofie","year":"2019","journal-title":"Comput Biol Med"},{"key":"B49","doi-asserted-by":"publisher","first-page":"132761","DOI":"10.1016\/j.molstruc.2022.132761","article-title":"Synthesis, antimicrobial, anticancer activities, PASS prediction, molecular docking, molecular dynamics and pharmacokinetic studies of designed methyl \u03b1-D-glucopyranoside esters","volume":"1260","author":"Islam","year":"2022","journal-title":"J Mol Struct"},{"key":"B50","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1517\/17460441.2012.648612","article-title":"Going further than Lipinski\u2019s rule in drug design","volume":"7","author":"Walters","year":"2012","journal-title":"Expert Opin Drug Discov"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-177-2_19","article-title":"Molecular docking","author":"Morris","year":"2008","journal-title":"Mol Model Proteins"},{"key":"B52","doi-asserted-by":"publisher","first-page":"388","DOI":"10.6026\/97320630013388","article-title":"Molecular docking based screening of a simulated HIF-1 protein model for potential inhibitors","volume":"13","author":"Latha","year":"2017","journal-title":"Bioinformation"},{"key":"B53","doi-asserted-by":"publisher","first-page":"195","DOI":"10.22036\/pcr.2021.294078.1934","article-title":"Modified D-glucofuranoses as new black fungus protease inhibitors: Computational screening, docking, dynamics, and QSAR study","volume":"10","author":"Rahman","year":"2022","journal-title":"Phys Chem Res"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s43088-021-00117-8","article-title":"Investigating the binding affinity, molecular dynamics, and ADMET properties of 2, 3-dihydrobenzofuran derivatives as an inhibitor of fungi, bacteria, and virus protein","volume":"10","author":"Nath","year":"2021","journal-title":"Beni-Suef Univ J Basic Appl Sci"},{"key":"B55","first-page":"e27","article-title":"Pharmacokinetics: the dynamics of drug absorption, distribution, metabolism, and elimination","volume":"3","author":"Benet","year":"1996","journal-title":"Goodman Gilman\u2019s Pharmacol basis Ther"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2020.1796812","article-title":"Virtual screening, ADMET prediction and dynamics simulation of potential compounds targeting the main protease of SARS-CoV-2","volume":"39","author":"Yadav","year":"2021","journal-title":"J Biomol Struct Dyn"},{"key":"B57","doi-asserted-by":"publisher","first-page":"459","DOI":"10.7555\/JBR.35.20210111","article-title":"Target specificity of selective bioactive compounds in blocking \u03b1-dystroglycan receptor to suppress Lassa virus infection: an in silico approach","volume":"35","author":"Arefin","year":"2021","journal-title":"J Biomed Res"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2018.0131","article-title":"Drug target prioritization for Alzheimer\u2019s disease using protein interaction network analysis","volume":"22","author":"Podder","year":"2018","journal-title":"OMICS: A J Integr Biol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.11.1","article-title":"What has polar surface area ever done for drug discovery","volume":"3","author":"Clark","year":"2011","journal-title":"Future Med Chem"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.2174\/0929867329666221004104430","article-title":"Looking for SARS-coV-2 therapeutics through computational approaches","volume":"30","author":"Vincenzi","year":"2023","journal-title":"Curr Med Chem"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1007\/s11696-022-02067-6","article-title":"Modelling the DFT structural and reactivity study of feverfew and evaluation of its potential antiviral activity against COVID-19 using molecular docking and MD simulations","volume":"76","author":"Lakhera","year":"2022","journal-title":"Chem Pap"},{"key":"B62","volume-title":"Part I: Structure and function in the NMDA ligand binding domain. Part II: Comparison of paclitaxel analogs through molecular dynamics simulation; solution conformations of cyclic peptides","author":"Geballe","year":"2009"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.1c00353","article-title":"Control of nanoscale in situ protein unfolding defines network architecture and mechanics of protein hydrogels","volume":"15","author":"Hughes","year":"2021","journal-title":"ACS nano"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2023.1228865\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T08:12:27Z","timestamp":1695715947000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2023.1228865\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,25]]},"references-count":63,"alternative-id":["10.3389\/fonc.2023.1228865"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2023.1228865","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,25]]},"article-number":"1228865"}}