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The antiplasmodial activity was compared to previously reported DHPM based molecular hybrids. Dual mode of antiplasmodial action of the most active member has been evaluated through heme binding study and <jats:italic>in silico<\/jats:italic> docking in the active site of dihydrofolate enzymes (wild\u2010type as well as mutant). Favourable pharmacokinetic parameters were predicted in the ADMET evaluation. The new hybrids were also tested against a number of DNA and RNA viruses. No antiviral activity was found, except for one hybrid that showed mild inhibitory activity against two strains of cytomegalovirus (AD\u2010169 and Davis), The most active hybrid was found to be a selective inhibitor of the growth of <jats:italic>P. falciparum<\/jats:italic> as well as a modest inhibitor of varicella zoster virus in HEL cells. Cytotoxicity of all hybrids was assessed in HEL, HeLa, Vero, MDCK, and CRFK cell cultures.<\/jats:p>","DOI":"10.1002\/cmdc.202200031","type":"journal-article","created":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T02:14:41Z","timestamp":1645064081000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Quinoline\u2010Dihydropyrimidin\u20102(1<i>H<\/i>)\u2010one Hybrids: Synthesis, Biological Activity, and Mechanistic Studies"],"prefix":"10.1002","volume":"17","author":[{"family":"Parth","sequence":"first","affiliation":[{"name":"Department of Chemistry, Centre of Advanced Study Guru Nanak Dev University  Amritsar 143 005 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hardeep","family":"Kaur","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Centre of Advanced Study Guru Nanak Dev University  Amritsar 143 005 India"},{"name":"PG Department of Chemistry Khalsa College  Amritsar 143 005 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leentje","family":"Persoons","sequence":"additional","affiliation":[{"name":"KU Leuven Department of Microbiology Immunology and Transplantation Laboratory of Virology and Chemotherapy Rega Institute  Rega, Herestraat 49, box 1030 3000 Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graciela","family":"Andrei","sequence":"additional","affiliation":[{"name":"KU Leuven Department of Microbiology Immunology and Transplantation Laboratory of Virology and Chemotherapy Rega Institute  Rega, Herestraat 49, box 1030 3000 Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9752-3363","authenticated-orcid":false,"given":"Kamaljit","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Centre of Advanced Study Guru Nanak Dev University  Amritsar 143 005 India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,2]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2542-5196(21)00132-7"},{"key":"e_1_2_8_2_1","unstructured":"World Malaria Report2021. 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