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Cytotoxicity test revealed that some compounds have strong to moderate effect, while others displayed weak action against different cancer cell lines including, MCF\u20107, HepG2, A549, and HTC\u2010116. A549 carcinoma cell line exhibited higher sensitivity toward all synthesized candidates especially compounds <jats:bold>6a<\/jats:bold> and <jats:bold>8a<\/jats:bold> which offered the lowest IC<jats:sub>50<\/jats:sub> values 3.03 and 5.21\u2009\u03bcM, respectively, relative to the positive control doxorubicin with IC<jats:sub>50<\/jats:sub> value of 3.01\u2009\u03bcM. Compared to doxorubicin treatment, compounds <jats:bold>6a<\/jats:bold> and <jats:bold>8a<\/jats:bold> induced caspases\u20103, \u20108, and \u20109 activities and G2\/M growth arrest in A549 carcinoma cell line. The expression levels of p53 (tumor suppressor protein that in humans is encoded by the TP53 gene), Bax (apoptosis regulator protein in humans that is encoded by bax gene), and the Bax\/Bcl\u20102 ratio were all higher than those in doxorubicin\u2010treated cells (Bcl\u20102, B\u2010cell lymphoma 2, encoded in humans by the Bcl\u20102 gene). Additionally, compounds <jats:bold>6a<\/jats:bold> and <jats:bold>8a<\/jats:bold> appeared to exhibit higher selectivity against MCF\u201010 human breast normal cell line. The synthesized congeners could be considered as potent apoptotic inducers interfering with extrinsic and intrinsic apoptotic pathways. Moreover, compound <jats:bold>6a<\/jats:bold> was able to form complex with zinc ions as indicated by UV spectrophotometry which revealed its ability for being caspase activator. Molecular docking studies expected the interactions and binding modes of the synthesized inhibitors in the caspase\u20103 active site.<\/jats:p>","DOI":"10.1002\/ddr.21573","type":"journal-article","created":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T11:35:12Z","timestamp":1564054512000},"page":"933-947","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Anticancer activity of newly synthesized 1,1\u2010disubstituted cyclohexane\u20101\u2010carboxamides: in vitro caspases mediated apoptosis activators in human cancer cell lines and their molecular modeling"],"prefix":"10.1002","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2659-2764","authenticated-orcid":false,"given":"Walaa Hamada","family":"Abd\u2010Allah","sequence":"first","affiliation":[{"name":"Pharmaceutical Chemistry Department, College of Pharmaceutical Science and Drug Manufacturing Misr University for Science &amp; Technology  Giza Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asmaa","family":"Salman","sequence":"additional","affiliation":[{"name":"Department of Medicinal and Pharmaceutical Chemistry (Pharmacology Group) National Research Centre  Giza Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samah","family":"Sabry Saad","sequence":"additional","affiliation":[{"name":"Pharmaceutical Analytical Chemistry Department, College of Pharmaceutical Science and Drug Manufacturing Misr University for Science &amp; Technology  Giza Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,7,25]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2017.01.021"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.13005\/ojc\/340228"},{"key":"e_1_2_6_4_1","unstructured":"Ali K. 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