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Repurposing of FDA approved drugs against EGFR have shown beneficial effect against AD but are confined to quinazoline, quinoline and aminopyrimidines. Futuristically, the possibility of acquiring drug resistance mutation as seen in the case of cancer could also hamper AD treatment. To identify novel chemical scaffolds, we rooted on phytochemicals identified from plants such as <jats:italic>Acorus calamus<\/jats:italic>, <jats:italic>Bacopa monnieri<\/jats:italic>, <jats:italic>Convolvulus pluricaulis<\/jats:italic>, <jats:italic>Tinospora cordifloia<\/jats:italic>, and <jats:italic>Withania somnifera<\/jats:italic> that have well\u2010established records in the treatment of brain disorders. The rationale was to mimic the biosynthetic metabolite extension process observed in the plants for synthesizing new phytochemical derivates. Thus, novel compounds were designed computationally by fragment\u2010based method followed by extensive <jats:italic>in silico<\/jats:italic> analysis to pick potential phytochemical derivates.<\/jats:p><jats:p>PCD1, 8 and 10 were predicted to have better blood brain barrier permeability. ADMET and SoM analysis suggested that these PCDs exhibited druglike properties. Further simulation studies showed that PCD1 and PCD8 stably interact with EGFR and have the potential to be used even in cases of drug\u2010resistance mutations. With further experimental evidence, these PCDs could be leveraged as potential inhibitors of EGFR.<\/jats:p>","DOI":"10.1002\/cbdv.202300681","type":"journal-article","created":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T17:19:02Z","timestamp":1688404742000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Computational Fragment\u2010Based Design of Phytochemical Derivatives as EGFR Inhibitors"],"prefix":"10.1002","volume":"20","author":[{"given":"Gayathri","family":"Shama Bhat","sequence":"first","affiliation":[{"name":"Department of Biotechnology Manipal Institute of Technology, Manipal Academy of Higher Education  Manipal 576104 Karnataka India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fayaz","family":"Shaik Mohammad","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Manipal Institute of Technology, Manipal Academy of Higher Education  Manipal 576104 Karnataka India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,7,20]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2003.11.041"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00030.2015"},{"key":"e_1_2_9_3_1","unstructured":"National Institute of Aging \u201cWhat Are the Signs of Alzheimer's Disease?\u201d can be found under https:\/\/www.nia.nih.gov\/health\/what-are-signs-alzheimers-disease 2022 (accessed 1 February 2023)."},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12694"},{"key":"e_1_2_9_5_1","first-page":"1","volume":"10","author":"Fulop T.","year":"2018","journal-title":"Neurosci"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3505"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.120.119909"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9081887"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1208011109"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2022.101791"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/9895121"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00227"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-015-9369-x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA117.000490"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3109\/13506129.2013.791810"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-26-08867.2003"},{"key":"e_1_2_9_17_1","first-page":"770","volume":"10","author":"Yu P.","year":"2019","journal-title":"Aging"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-05058-3"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.332132"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2021.06.013"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26216677"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3747\/co.v18i3.877"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-022-01311-6"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/esmoopen-2016-000060"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.4062\/biomolther.2021.047"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1590\/0001-3765201920190105"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-020-00114-z"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00397"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24234309"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-018-0216-7"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871527320666210920120612"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.8b00458"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11030-022-10506-5"},{"key":"e_1_2_9_34_1","first-page":"231","volume-title":"Homology Modeling","author":"Kufareva I.","year":"2012"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddtec.2010.11.003"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm100087s"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.1c00302"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-22631-z"},{"key":"e_1_2_9_39_1","unstructured":"A.\u2005R.\u2005S.\u2005U.\u2005S. 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