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A highly efficient bifunctionalized amino catalyst is developed to access structurally diverse\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010indolyl ketones in high yields (up to 91%) and excellent enantioselectivity (enantiomeric ratio up to 98:2). All the synthesized compounds demonstrated promising aromatase inhibitory potential, where\n                    <jats:italic>ortho<\/jats:italic>\n                    \u2010substituted analogs (\n                    <jats:bold>3c<\/jats:bold>\n                    and\n                    <jats:bold>3e<\/jats:bold>\n                    ) were found most active with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 0.68 and 0.90\u2009\u00b5M, respectively. Both of these compounds exhibited significant cytotoxicity (IC\n                    <jats:sub>50\u2009<\/jats:sub>\n                    =\u20090.34 and 0.37\u2009\u00b5M) against the MCF\u20107 breast cancer cell line in the (3\u2010[4,5\u2010dimethylthiazol\u20102\u2010yl]\u20102,5\u2010diphenyl tetrazolium bromide) assay. Molecular docking studies of the synthesized compounds demonstrate favorable binding interactions with the estrogens controlling CYP19A1 (3EQM) and metabolizing CYP3A4 (5VCC) enzymes. Molecular dynamic (MD) simulation analysis revealed the essentiality of heme\u2013ligand interactions to build a stable protein\u2013ligand complex. An average root mean square deviation of 0.35\u2009nm observed during a 100\u2010ns MD simulation and binding free energy in the range of \u2212190 to \u2212227\u2009kJ\/mol calculated by g_mmpbsa analysis authenticated the stability of the\n                    <jats:bold>3c<\/jats:bold>\n                    \u20133EQM complex. ADMET and drug\u2010likeness parameters supported the suitability of these indole derivatives as the drug lead to develop potent inhibitors for estrogen\u2010dependent breast cancer.\n                  <\/jats:p>","DOI":"10.1002\/ardp.202400010","type":"journal-article","created":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T08:44:59Z","timestamp":1712306699000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["New enantioenriched\n                    <i>\u03b2<\/i>\n                    \u2010indolyl ketones as aromatase inhibitors: Unraveling heme\u2013ligand interactions by MD simulation\u00a0and MMPBSA analysis"],"prefix":"10.1002","volume":"357","author":[{"given":"Maira Hasnain","family":"Pasha","sequence":"first","affiliation":[{"name":"Institute of Chemistry, Faculty of Science University of Sargodha Sargodha Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9532-681X","authenticated-orcid":false,"given":"Humaira Yasmeen","family":"Gondal","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, Faculty of Science University of Sargodha Sargodha Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanza","family":"Munir","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, Faculty of Science University of Sargodha Sargodha Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sami A.","family":"Alhussain","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science Imam Mohammad Ibn Saud Islamic University (IMSIU) Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdi E. 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