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Currently, there are sizeable therapeutic disquiets with the use of synthetic histone deacetylase inhibitors in disease management. This strongly suggests the unfulfilled medical necessity of plant substitutes for therapeutic intervention. Sulforaphane\u2010N\u2010acetyl\u2010cysteine (SFN\u2010N\u2010acetylcysteine or SFN\u2010NAC), a sulforaphane metabolite has shown significantly worthier activity against HDACs under <jats:italic>in vitro<\/jats:italic> conditions. However, the atomistic studies of SFN\u2010NAC against HDAC2 are currently lacking. Thus, the present study employed a hybrid strategy including extra\u2010precision (XP) grid\u2010based flexible molecular docking, molecular mechanics generalized born surface area (MM\u2010GBSA), e\u2010Pharmacophores method, and molecular dynamics simulation for exploring the binding strengh, mode of interaction, e\u2010Pharmacophoric features, and stability of SFN\u2010NAC towards HDAC2. Further, the globally acknowledged density functional theory (DFT) study was performed on SFN\u2010NAC and entinostat individually in complex state with HDAC2. Apart from this, these inhibitors  were tested against three distinct cancer cell models and one transformed cell line for cytotoxic activity. Moreover, double mutant of HDAC2 was generated and the binding orientation and interaction of SFN\u2010NAC was scrutinized in this state. On the whole, this study unbosomed and explained the comparatively higher binding affinity of entinostat for HDAC2 and its wide spectrum cytotoxicity than SFN\u2010NAC.<\/jats:p>","DOI":"10.1111\/cbdd.13854","type":"journal-article","created":{"date-parts":[[2021,5,9]],"date-time":"2021-05-09T13:34:56Z","timestamp":1620567296000},"page":"363-376","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Delineating binding potential, stability of Sulforaphane\u2010N\u2010acetyl\u2010cysteine  in the active site of histone deacetylase 2 and testing its cytotoxicity against distinct cancer lines through stringent molecular dynamics, DFT and cell\u2010based assays"],"prefix":"10.1111","volume":"98","author":[{"given":"Shabir Ahmad","family":"Ganai","sequence":"first","affiliation":[{"name":"Division of Basic Sciences and Humanities FoA SKUAST\u2010Kashmir  193201 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pappu","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"Department of Animal Health and Management Alagappa University  Karaikudi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sundaraj","family":"Rajamanikandan","sequence":"additional","affiliation":[{"name":"ICAR\u2010National Institute of Veterinary Epidemiology and Disease Informatics  Bengaluru India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Basit Amin","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Biotechnology University of Kashmir  Srinagar India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suma","family":"Mohan","sequence":"additional","affiliation":[{"name":"SCBT Shanmugha Arts Science Technology and Research Academy  613401 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mudasir","family":"Gani","sequence":"additional","affiliation":[{"name":"Division of Entomology FoA SKUAST\u2010Kashmir  193201 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bilal Ahmad","family":"Padder","sequence":"additional","affiliation":[{"name":"Division of Plant Pathology FoH, SKUAST\u2010Kashmir  190025 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raies A.","family":"Qadri","sequence":"additional","affiliation":[{"name":"Department of Biotechnology University of Kashmir  Srinagar India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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