{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T01:20:12Z","timestamp":1777425612604,"version":"3.51.4"},"reference-count":47,"publisher":"Portland Press Ltd.","issue":"10","license":[{"start":{"date-parts":[[2020,5,13]],"date-time":"2020-05-13T00:00:00Z","timestamp":1589328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,5,29]]},"abstract":"<jats:p>Upon Plasmodium falciparum merozoites exposure to low [K+] environment in blood plasma, there is escalation of cytosolic [Ca2+] which activates Ca2+-Dependent Protein Kinase 1 (CDPK1), a signaling hub of intra-erythrocytic proliferative stages of parasite. Given its high abundance and multidimensional attributes in parasite life-cycle, this is a lucrative target for designing antimalarials. Towards this, we have virtually screened MyriaScreenII diversity collection of 10,000 drug-like molecules, which resulted in 18 compounds complementing ATP-binding pocket of CDPK1. In vitro screening for toxicity in mammalian cells revealed that these compounds are non-toxic in nature. Furthermore, SPR analysis demonstrated differential binding affinity of these compounds towards recombinantly purified CDPK1 protein. Selection of lead compound 1 was performed by evaluating their inhibitory effects on phosphorylation and ATP binding activities of CDPK1. Furthermore, in vitro biophysical evaluations by ITC and FS revealed that binding of compound 1 is driven by formation of energetically favorable non-covalent interactions, with different binding constants in presence and absence of Ca2+, and TSA authenticated stability of compound 1 bound CDPK1 complex. Finally, compound 1 strongly inhibited intra-erythrocytic growth of P. falciparum in vitro. Conceivably, we propose a novel CDPK1-selective inhibitor, step towards developing pan-CDPK kinase inhibitors, prerequisite for cross-stage anti-malarial protection.<\/jats:p>","DOI":"10.1042\/bcj20200045","type":"journal-article","created":{"date-parts":[[2020,5,13]],"date-time":"2020-05-13T21:24:14Z","timestamp":1589405054000},"page":"1951-1970","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Development of novel anti-malarial from structurally diverse library of molecules, targeting plant-like CDPK1, a multistage growth regulator of\n                    <i>P. falciparum<\/i>"],"prefix":"10.1042","volume":"477","author":[{"given":"Ravi","family":"Jain","sequence":"first","affiliation":[{"name":"Department of Life Sciences, School of Natural Sciences, Shiv Nadar University, Gautam Buddha Nagar, UP 201314, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sakshi","family":"Gupta","sequence":"additional","affiliation":[{"name":"School of Physical Sciences, Jawaharlal Nehru University, Delhi 110067, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manoj","family":"Munde","sequence":"additional","affiliation":[{"name":"School of Physical Sciences, Jawaharlal Nehru University, Delhi 110067, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soumya","family":"Pati","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, School of Natural Sciences, Shiv Nadar University, Gautam Buddha Nagar, UP 201314, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5286-6605","authenticated-orcid":false,"given":"Shailja","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, School of Natural Sciences, Shiv Nadar University, Gautam Buddha Nagar, UP 201314, India"},{"name":"Special Center for Molecular Medicine, Jawaharlal Nehru University, Delhi 110067, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2020,5,29]]},"reference":[{"key":"2021112218092013700_BCJ-2020-0045C1","unstructured":"2018, W. malaria report. 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