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Compounds <jats:bold>9a\u2013c<\/jats:bold> exhibited broad\u2010spectrum activity with low micromolar EC<jats:sub>50<\/jats:sub> values toward wild and mutant varicella\u2010zoster virus (VZV) strains. Compound <jats:bold>9b<\/jats:bold> was up to threefold more potent than the reference drug acyclovir against thymidine kinase\u2010deficient VZV strains. Importantly, derivative <jats:bold>9b<\/jats:bold> was not cytostatic at the maximum tested concentration (CC<jats:sub>50<\/jats:sub>\u2009&gt;\u2009100\u2009\u00b5M) and had an acceptable selectivity index value of up to 7.8. Moreover, all synthesized 1,3,4\u2010oxadiazole hybrids were evaluated for their cytotoxic activity in four human cancer cell lines: fibrosarcoma (HT\u20101080), breast (MCF\u20107 and MDA\u2010MB\u2010231), and lung carcinoma (A549). Data showed that compound <jats:bold>8f<\/jats:bold> exhibits moderate cytotoxicity, with IC<jats:sub>50<\/jats:sub> values ranging from 13.89 to 19.43\u2009\u00b5M. Besides, compound <jats:bold>8f<\/jats:bold> induced apoptosis through caspase 3\/7 activation, cell death independently of the mitochondrial pathway, and cell cycle arrest in the S phase for HT1080 cells and the G1\/M phase for A549 cells. Finally, the molecular docking study confirmed that the anticancer activity of the synthesized compounds is mediated by the activation of caspase 3.<\/jats:p>","DOI":"10.1002\/ardp.202100146","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T07:14:42Z","timestamp":1623741282000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Discovery of novel furo[2,3\u2010<i>d<\/i>]pyrimidin\u20102\u2010one\u20131,3,4\u2010oxadiazole hybrid derivatives as dual antiviral and anticancer agents that induce apoptosis"],"prefix":"10.1002","volume":"354","author":[{"given":"Az\u2010eddine","family":"El Mansouri","sequence":"first","affiliation":[{"name":"Laboratory of Biomolecular and Medicinal Chemistry, Chemistry Department, Faculty of Science Semlalia University Cadi Ayyad  Marrakesh Morocco"},{"name":"Laboratoire de Mat\u00e9riaux, Catalyse &amp; Valorisation des Ressources Naturelles, URAC 24, Department de chimie, Facult\u00e9 des Sciences et Techniques Universit\u00e9 Hassan II  Casablanca Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Oubella","sequence":"additional","affiliation":[{"name":"Laboratoire de Synthese Organique et de Physico\u2010Chimie Moleculaire, Departement de Chimie Facult\u00e9 des Sciences Semlalia  Marrakech Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"D\u00e2noun","sequence":"additional","affiliation":[{"name":"MASCIR Foundation Rabat Design Rue Mohamed El Jazouli, Madinat El Irfane, 10100 Rabat, Morocco Rabat Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Ahmad","sequence":"additional","affiliation":[{"name":"ICGM Universit\u00e9 Montpellier, CNRS, ENSCM  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Neyts","sequence":"additional","affiliation":[{"name":"Rega Institute for Medical Research KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Jochmans","sequence":"additional","affiliation":[{"name":"Rega Institute for Medical Research KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Snoeck","sequence":"additional","affiliation":[{"name":"Rega Institute for Medical Research KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graciela","family":"Andrei","sequence":"additional","affiliation":[{"name":"BioSpecT\u2014EA7506 UFR de Pharmacie  Reims France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid","family":"Morjani","sequence":"additional","affiliation":[{"name":"BioSpecT\u2014EA7506 UFR de Pharmacie  Reims France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Zahouily","sequence":"additional","affiliation":[{"name":"Laboratoire de Mat\u00e9riaux, Catalyse &amp; Valorisation des Ressources Naturelles, URAC 24, Department de chimie, Facult\u00e9 des Sciences et Techniques Universit\u00e9 Hassan II  Casablanca Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3849-9092","authenticated-orcid":false,"given":"Hassan B.","family":"Lazrek","sequence":"additional","affiliation":[{"name":"Laboratory of Biomolecular and Medicinal Chemistry, Chemistry Department, Faculty of Science Semlalia University Cadi Ayyad  Marrakesh Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,6,15]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/canjclin.57.1.43"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199957020-00005"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/1573406413666170307165236"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2016.06.051"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7878464"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm990412m"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.9b00338"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2662"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01220"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.3109\/13550281003682547"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.9.2951"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(02)00788-X"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr000446y"},{"key":"e_1_2_7_15_1","first-page":"405","volume":"881","author":"Yang R. 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