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Compounds <jats:bold>8\u2009g<\/jats:bold> (IC<jats:sub>50<\/jats:sub>=0.051\u2005\u03bcM; SI=589.41) and <jats:bold>8\u2009m<\/jats:bold> (IC<jats:sub>50<\/jats:sub>=0.059\u2005\u03bcM; SI=55.93) showed 11\u2010fold and &gt;9\u2010fold more potent antiplasmodial activity, respectively, as compared to chloroquine (IC<jats:sub>50<\/jats:sub>=0.546\u2005\u03bcM; SI=36.63). Different <jats:italic>in silico<\/jats:italic> docking studies performed on many target proteins revealed that the most active arylvinyl\u20101,2,4\u2010trioxanes (<jats:bold>8\u2009g<\/jats:bold> and <jats:bold>8\u2009m<\/jats:bold>) showed dihydrofolate reductase (DHFR) binding affinities on a par with those of chloroquine and artesunate. The <jats:italic>in\u2005vitro<\/jats:italic> cytotoxic potentials of <jats:bold>8\u2009a<\/jats:bold>\u2013<jats:bold>p<\/jats:bold> were also evaluated against human lung (A549) and liver (HepG2) cancer cell lines along with immortalized normal lung (BEAS\u20102B) and liver (LO2) cell lines. Following screening, five derivatives viz. <jats:bold>8\u2009a<\/jats:bold>, <jats:bold>8\u2009h<\/jats:bold>, <jats:bold>8\u2009l<\/jats:bold>, <jats:bold>8\u2009m<\/jats:bold> and <jats:bold>8\u2009o<\/jats:bold> (IC<jats:sub>50<\/jats:sub>=1.65\u201331.7\u2005\u03bcM; SI=1.08\u201310.96) were found to show potent cytotoxic activity against (A549) lung cancer cell lines, with selectivity superior to that of the reference compounds artemisinin (IC<jats:sub>50<\/jats:sub>=100\u2005\u03bcM), chloroquine (IC<jats:sub>50<\/jats:sub>=100\u2005\u03bcM) and artesunic acid (IC<jats:sub>50<\/jats:sub>=9.85\u2005\u03bcM; SI=0.76). In fact, the most active 4\u2010naphthyl\u2010substituted analogue <jats:bold>8\u2009l<\/jats:bold> (IC<jats:sub>50<\/jats:sub>=1.65\u2005\u03bcM; SI &gt;10) exhibited &gt;60 times more cytotoxicity than the standard reference, artemisinin, against A549 lung cancer cell lines. <jats:italic>In silico<\/jats:italic> docking studies of the most active anticancer compounds, <jats:bold>8\u2009l<\/jats:bold> and <jats:bold>8\u2009m<\/jats:bold>, against EGFR were found to validate the wet lab results. In summary, a new series of functionalized aryl\u2010vinyl\u20101,2,4\u2010trioxanes (<jats:bold>8\u2009a<\/jats:bold>\u2013<jats:bold>p<\/jats:bold>) has been shown to display dual potency as promising antiplasmodial and anticancer agents.<\/jats:p>","DOI":"10.1002\/cmdc.202000045","type":"journal-article","created":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T15:06:47Z","timestamp":1589209607000},"page":"1216-1228","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Design, Synthesis, Structure\u2010Activity Relationship and Docking Studies of Novel Functionalized Arylvinyl\u20101,2,4\u2010Trioxanes as Potent Antiplasmodial as well as Anticancer Agents"],"prefix":"10.1002","volume":"15","author":[{"given":"Mohit K.","family":"Tiwari","sequence":"first","affiliation":[{"name":"Laboratory of Organic and Medicinal Chemistry Department of Chemistry Malaviya National Institute of Technology  Jawaharlal Nehru Marg Jaipur 302017 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Coghi","sequence":"additional","affiliation":[{"name":"School of Pharmacy Macau University of Science and Technology  Avenida wai long Taipa Macau China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakhar","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Malaria Drug Discovery Laboratory International Centre for Genetic Engineering and Biotechnology  Aruna Asaf Ali Marg 110 067 New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharti Rajesh K.","family":"Shyamlal","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Medicinal Chemistry Department of Chemistry Malaviya National Institute of Technology  Jawaharlal Nehru Marg Jaipur 302017 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jun Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Quality Research in Chinese Medicine Macau University of Science and Technology  Avenida Wai Long Taipa Macau China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lalit","family":"Yadav","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Medicinal Chemistry Department of Chemistry Malaviya National Institute of Technology  Jawaharlal Nehru Marg Jaipur 302017 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhong","family":"Peng","sequence":"additional","affiliation":[{"name":"School of Pharmacy Macau University of Science and Technology  Avenida wai long Taipa Macau China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richa","family":"Sharma","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Medicinal Chemistry Department of Chemistry Malaviya National Institute of Technology  Jawaharlal Nehru Marg Jaipur 302017 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dharmendra K.","family":"Yadav","sequence":"additional","affiliation":[{"name":"College of Pharmacy Gachon University of Medicine and Science  Hambakmoeiro 191, Yeonsu-gu Incheon city 406-799 South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinkar","family":"Sahal","sequence":"additional","affiliation":[{"name":"Malaria Drug Discovery Laboratory International Centre for Genetic Engineering and Biotechnology  Aruna Asaf Ali Marg 110 067 New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Kam Wai Wong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Quality Research in Chinese Medicine Macau University of Science and Technology  Avenida Wai Long Taipa Macau China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1444-3895","authenticated-orcid":false,"given":"Sandeep","family":"Chaudhary","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Medicinal Chemistry Department of Chemistry Malaviya National Institute of Technology  Jawaharlal Nehru Marg Jaipur 302017 India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,3]]},"reference":[{"key":"e_1_2_8_1_1","unstructured":"World Malaria Report: 2018. 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