{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:56:07Z","timestamp":1788998167574,"version":"build-2803163510"},"reference-count":65,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/INF\/22\/SP42545\/2021"],"award-info":[{"award-number":["BT\/INF\/22\/SP42545\/2021"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["DBT\/2019\/IBAB\/1183"],"award-info":[{"award-number":["DBT\/2019\/IBAB\/1183"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","award":["CRG\/2020\/004801"],"award-info":[{"award-number":["CRG\/2020\/004801"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aces.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry \u0097 An Asian Journal"],"published-print":{"date-parts":[[2025,3,17]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In this study, we built on the known inhibitory potential of diaminoquinazolines (DAQs) against different stages of <jats:italic>Plasmodium<\/jats:italic> development and designed a convenient two\u2010step synthesis to combine DAQ with primaquine (PQ) pharmacophore. The PQ\u2010DAQ hybrids displayed potent <jats:italic>in\u2005vitro<\/jats:italic> activities in the low nanomolar range (IC<jats:sub>50<\/jats:sub> 135.20\u2013398.80\u2005nM) against all intra\u2010erythrocytic stages of the drug\u2010sensitive 3D7 strain, with significant potency enhancement compared to PQ alone (IC<jats:sub>50<\/jats:sub> 9370\u2005nM). These hybrids were also potent at killing drug\u2010resistant strains (Dd2, Dd2\u2002R539T, IPC4912, CamWT\u2002C580Y, and 7G8) in the nanomolar range, with <jats:bold>11\u2009f<\/jats:bold> being the most effective compound (IC<jats:sub>50<\/jats:sub> 172.20\u2013396.60\u2005nM). Notably, for the first time, we present evidence that the DAQ\u2010based compound <jats:bold>8<\/jats:bold> and its hybrids can inhibit <jats:italic>\u03b2<\/jats:italic>\u2010hematin formation <jats:italic>in\u2005vitro<\/jats:italic> with potency (IC<jats:sub>50<\/jats:sub> 0.90\u201327.80\u2005\u03bcM), suggesting hemozoin formation to be one of the potential targets of this series. Lastly, two hybrids with potent antiplasmodial activity were also found to be safe up to 10\u2005\u03bcM against human HepG2 cells, suggesting the possibility of achieving host <jats:italic>vs<\/jats:italic> parasite selectivity with this series.<\/jats:p>","DOI":"10.1002\/asia.202401366","type":"journal-article","created":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T08:18:42Z","timestamp":1736324322000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Design, Synthesis and <i>in\u2005vitro<\/i> Evaluation of Primaquine and Diaminoquinazoline Hybrid Molecules Against the Malaria Parasite"],"prefix":"10.1002","volume":"20","author":[{"given":"Mukul","family":"Kore","sequence":"first","affiliation":[{"name":"Department of Pharmacy Birla Institute of Technology and Science Pilani  Pilani Campus Rajasthan 333031 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjani G.","family":"Rao","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics and Applied Biotechnology  Helix Biotech Park, Electronics City Phase I Bengaluru Karnataka 560100 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimple","family":"Acharya","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics and Applied Biotechnology  Helix Biotech Park, Electronics City Phase I Bengaluru Karnataka 560100 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shrikant S.","family":"Kirwale","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Birla Institute of Technology and Science Pilani  Pilani Campus Rajasthan 333031 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amritansh","family":"Bhanot","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Birla Institute of Technology and Science Pilani  Pilani Campus Rajasthan 333031 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek","family":"Govekar","sequence":"additional","affiliation":[{"name":"ICMR-National Institute of Malaria Research  Field Unit, DHS Building, Campal Panaji Goa 403001 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajeet Kumar","family":"Mohanty","sequence":"additional","affiliation":[{"name":"ICMR-National Institute of Malaria Research  Field Unit, DHS Building, Campal Panaji Goa 403001 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3374-421X","authenticated-orcid":false,"given":"Aniruddha","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Birla Institute of Technology and Science Pilani  Pilani Campus Rajasthan 333031 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7497-6378","authenticated-orcid":false,"given":"Shruthi S.","family":"Vembar","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics and Applied Biotechnology  Helix Biotech Park, Electronics City Phase I Bengaluru Karnataka 560100 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7823-8842","authenticated-orcid":false,"given":"Sandeep","family":"Sundriyal","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Birla Institute of Technology and Science Pilani  Pilani Campus Rajasthan 333031 India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,24]]},"reference":[{"key":"e_1_2_9_1_1","unstructured":"WHO World Malaria Report2024 2024."},{"key":"e_1_2_9_2_1","unstructured":"World Health Organization WHO Guidelines for malaria 2022."},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(19)30392-5"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30635-7"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpha.2020.07.005"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-019-2724-z"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1517\/17460441.2016.1135125"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2016.08.039"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.21643"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm300802s"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules22122268"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.20345"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr500123g"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113408"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.4.1329-1334.2004"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01472-05"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11239-0"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-12-408"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05133-11"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2019.08.018"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijmm.2013.07.005"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26133991"},{"key":"e_1_2_9_23_1","author":"Kaur H.","journal-title":"Eur. J. Med. Chem."},{"key":"e_1_2_9_24_1","author":"Pavi\u0107 K.","journal-title":"Eur. J. Med. Chem."},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.01.017"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2008.01.002"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2011.11.011"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep21802"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1205414109"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201402098"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.7b00228"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04419-14"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7MD00052A"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4MD00274A"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.1c00104"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c00206"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201402098"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.13.113"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2003.08.009"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.9.2784"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1700125114"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1501023112"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202200139"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.4c01154"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.2174\/138620710790980496"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00121-11"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2014.08.002"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-29273-w"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/cg025550i"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms12122524"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1074045"},{"key":"e_1_2_9_52_1","doi-asserted-by":"crossref","unstructured":"S.\u2005K. Dhingra S.\u2005J. Gabryszewski J.\u2005L. Small-Saunders T. Yeo P.\u2005P. Henrich S. Mok and D.\u2005A. Fidock 2019. Global Spread of Mutant PfCRT and Its Pleiotropic Impact on Plasmodium falciparum Multidrug Resistance and Fitness. https:\/\/doi.org\/10.1128\/mbio.02731-18","DOI":"10.1128\/mBio.02731-18"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2022.10.003"},{"key":"e_1_2_9_54_1","doi-asserted-by":"crossref","DOI":"10.1128\/aac.01189-23","volume":"68","author":"Ahmed A. O. A.","year":"2024","journal-title":"Antimicrob. Agents Chemother."},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.3347\/kjp.2022.60.6.401"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202000653"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(87)90175-1"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-015-1053-0"},{"key":"e_1_2_9_59_1","unstructured":"World Health Organization In vitromicro-test (Mark III) for the assessment of the response ofPlasmodium falciparumto chloroquine mefloquine quinine amodiaquine sulfadoxine\/pyrimethamine and artemisinin instructions for use of thein\u2005vitromicro-test kit (Mark III) World Health Organization Geneva PP - Geneva 2nd rev. 2001."},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(13)70252-4"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/35005132"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889811038970"},{"key":"e_1_2_9_63_1","doi-asserted-by":"crossref","unstructured":"S. Dallakyan and A.\u2005J. Olson in Methods in Molecular Biology Humana Press Inc. 2015 vol. 1263 pp. 243\u2013250.","DOI":"10.1007\/978-1-4939-2269-7_19"},{"key":"e_1_2_9_64_1","first-page":"2967","volume":"31","author":"Trott O.","year":"2009","journal-title":"J. Comput. Chem."},{"key":"e_1_2_9_65_1","unstructured":"Schr\u00f6dinger Release 2022\u20132: LigPrep Schr\u00f6dinger LLC New York NY. 2021."}],"container-title":["Chemistry \u2013 An Asian Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aces.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/asia.202401366","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T18:24:26Z","timestamp":1759947866000},"score":1,"resource":{"primary":{"URL":"https:\/\/aces.onlinelibrary.wiley.com\/doi\/10.1002\/asia.202401366"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,24]]},"references-count":65,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,3,17]]}},"alternative-id":["10.1002\/asia.202401366"],"URL":"https:\/\/doi.org\/10.1002\/asia.202401366","archive":["Portico"],"relation":{},"ISSN":["1861-4728","1861-471X"],"issn-type":[{"value":"1861-4728","type":"print"},{"value":"1861-471X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,24]]},"assertion":[{"value":"2024-10-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202401366"}}