{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T22:39:26Z","timestamp":1787611166533,"version":"build-2736575974"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2020,8,27]],"date-time":"2020-08-27T00:00:00Z","timestamp":1598486400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"DOI":"10.1371\/journal.pntd.0008489","type":"journal-article","created":{"date-parts":[[2020,8,27]],"date-time":"2020-08-27T17:26:41Z","timestamp":1598549201000},"page":"e0008489","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["In vitro and in vivo growth inhibitory activities of cryptolepine hydrate against several Babesia species and Theileria equi"],"prefix":"10.1371","volume":"14","author":[{"given":"Gaber El-Saber","family":"Batiha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amany Magdy","family":"Beshbishy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luay M.","family":"Alkazmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman H.","family":"Nadwa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman K.","family":"Rashwan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoaki","family":"Yokoyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4361-3942","authenticated-orcid":true,"given":"Ikuo","family":"Igarashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,8,27]]},"reference":[{"issue":"4","key":"pntd.0008489.ref001","doi-asserted-by":"crossref","first-page":"996","DOI":"10.3390\/molecules25040996","article-title":"Phytochemical characterization and chemotherapeutic potential of Cinnamomum verum extracts on the multiplication of protozoan parasites in vitro and in vivo","volume":"25","author":"GE-S Batiha","year":"2020a","journal-title":"Molecules"},{"issue":"2","key":"pntd.0008489.ref002","doi-asserted-by":"crossref","first-page":"E127","DOI":"10.3390\/pathogens9020127","article-title":"Therapeutic effects of atranorin towards the proliferation of Babesia and Theileria parasites","volume":"9","author":"AM Beshbishy","year":"2020","journal-title":"Pathogen"},{"key":"pntd.0008489.ref003","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1292\/jvms.12-0056","article-title":"Involvement of mitochondrial genes of Babesia gibsoni in resistance to diminazene aceturate","volume":"74","author":"BKW Rajapakshage","year":"2012","journal-title":"J Vet Med Sci"},{"key":"pntd.0008489.ref004","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s13071-014-0611-6","article-title":"Theileria equi isolates vary in susceptibility to imidocarb dipropionate but demonstrate uniform in vitro susceptibility to a bumped kinase inhibitor","volume":"8","author":"SA Hines","year":"2015","journal-title":"Parasite Vectors"},{"key":"pntd.0008489.ref005","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1128\/CMR.16.4.622-636.2003","article-title":"Babesia divergens, a bovine blood parasite of veterinary and zoonotic importance","volume":"16","author":"A Zintl","year":"2003","journal-title":"Clin Microbiol Rev"},{"key":"pntd.0008489.ref006","doi-asserted-by":"crossref","first-page":"550","DOI":"10.3390\/molecules25030550","article-title":"Phytochemical screening and antiprotozoal effects of the methanolic Berberis vulgaris and acetonic Rhus coriaria extracts","volume":"25","author":"GE-S Batiha","year":"2020b","journal-title":"Molecules"},{"key":"pntd.0008489.ref007","first-page":"137","article-title":"A review of the anticancer potential of the antimalarial herbal Cryptolepis sanguinolenta and its major alkaloid cryptolepine","volume":"47","author":"C Ansah","year":"2013","journal-title":"Ghana Med J"},{"key":"pntd.0008489.ref008","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1021\/jm9704816","article-title":"Ethnobotanical-directed discovery of the antihyperglycemic properties of cryptolepine: Its isolation from Cryptolepis sanguinolenta, synthesis, and in vitro and in vivo activities","volume":"41","author":"DE Bierer","year":"1998","journal-title":"J Med Chem"},{"key":"pntd.0008489.ref009","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/j.1472-765X.2004.01625.x","article-title":"The killing effect of cryptolepine on Staphylococcus aureus","volume":"40","author":"IK Sawer","year":"2005","journal-title":"Lett Applied Microbiol"},{"key":"pntd.0008489.ref010","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0014-2999(95)00289-W","article-title":"Cryptolepine-induced vasodilation in the isolated perfused kidney of the rat: role of G-proteins, K+ and Ca2+ channels","volume":"285","author":"AO Oyekan","year":"1995","journal-title":"Europ J Pharmacol"},{"key":"pntd.0008489.ref011","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1002\/ptr.1284","article-title":"Cryptolepine hydrochloride: a potent antimycobacterial alkaloid derived from Cryptolepis sanguinolenta","volume":"17","author":"S Gibbons","year":"2003","journal-title":"Phytother Res"},{"key":"pntd.0008489.ref012","doi-asserted-by":"crossref","first-page":"3187","DOI":"10.1021\/jm010929+","article-title":"Synthesis and evaluation of cryptolepine analogues for their potential as new antimalarial agents","volume":"44","author":"CW Wright","year":"2001","journal-title":"J Med Chem"},{"key":"pntd.0008489.ref013","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s12936-016-1137-5","article-title":"Synergistic anti-malarial action of cryptolepine and artemisinins","volume":"15","author":"AD Forkuo","year":"2016","journal-title":"Malaria J"},{"key":"pntd.0008489.ref014","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1016\/j.bcp.2003.08.009","article-title":"Inhibition of heme crystal growth by antimalarials and other compounds: implication for drug discovery","volume":"66","author":"CR Chong","year":"2003","journal-title":"Biochem Pharmacol"},{"key":"pntd.0008489.ref015","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1021\/jm101383f","article-title":"Incorporation of basic side chains into cryptolepine scaffold: structure-antimalarial activity relationships and mechanistic studies","volume":"54","author":"J Lavrado","year":"2011","journal-title":"J Med Chem"},{"key":"pntd.0008489.ref016","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1002\/ptr.2794","article-title":"Anti-inflammatory properties of cryptolepine","volume":"23","author":"OA Olajide","year":"2009","journal-title":"Phytother Res"},{"key":"pntd.0008489.ref017","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.ejmech.2013.02.004","article-title":"Anti-neuroinflammatory properties of synthetic cryptolepine in human neuroblastoma cells: possible involvement of NF-\u03baB and p38 MAPK inhibition","volume":"63","author":"OA Olajide","year":"2013","journal-title":"European J Med Chem"},{"key":"pntd.0008489.ref018","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.3390\/molecules21121758","article-title":"Cryptolepine, a plant alkaloid, inhibits the growth of non-melanoma skin cancer cells through inhibition of topoisomerase and induction of DNA damage","volume":"21","author":"HC Pal","year":"2016","journal-title":"Molecules"},{"key":"pntd.0008489.ref019","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nsb729","article-title":"The antimalarial and cytotoxic drug cryptolepine intercalates into DNA at cytosine-cytosine sites","volume":"9","author":"JN Lisgarten","year":"2002","journal-title":"Nature Struct Biol"},{"key":"pntd.0008489.ref020","first-page":"1","article-title":"Botanicals for treatment of babesiosis and theileriosis","volume":"2","author":"R Ravindran","year":"2017","journal-title":"Annals Pharmacol Pharmaceut"},{"key":"pntd.0008489.ref021","first-page":"1","article-title":"Inhibitory effects of Uncaria tomentosa bark, Myrtus communis roots, Origanum vulgare leaves and Cuminum cyminum seeds extracts against the growth of Babesia and Theileria in vitro","volume":"17","author":"GE-S Batiha","year":"2018","journal-title":"Jap J Vet Parasit"},{"key":"pntd.0008489.ref022","doi-asserted-by":"crossref","first-page":"6256","DOI":"10.1016\/j.bmcl.2012.07.104","article-title":"Antitrypanosomal and cysteine protease inhibitory activities of alkyl diamine cryptolepine derivatives","volume":"22","author":"J Lavrado","year":"2012","journal-title":"Bioorgan Med Chem Lett"},{"key":"pntd.0008489.ref023","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s00436-012-2818-9","article-title":"Antileishmanial activity of cryptolepine analogues and apoptotic effects of 2, 7-dibromocryptolepine against Leishmania donovani promastigotes","volume":"111","author":"S Hazra","year":"2012","journal-title":"Parasitol Res"},{"key":"pntd.0008489.ref024","doi-asserted-by":"crossref","first-page":"187850","DOI":"10.4061\/2011\/187850","article-title":"Cryptolepine-induced cell death of Leishmania donovani promastigotes is augmented by inhibition of autophagy","volume":"2011","author":"S Sengupta","year":"2011","journal-title":"Mol Biol Inter"},{"key":"pntd.0008489.ref025","doi-asserted-by":"crossref","first-page":"2701","DOI":"10.1021\/jm040893w","article-title":"Synthesis of some cryptolepine analogues, assessment of their antimalarial and cytotoxic activities, and consideration of their antimalarial mode of action","volume":"48","author":"O Onyeibor","year":"2005","journal-title":"J Med Chem"},{"key":"pntd.0008489.ref026","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s40360-017-0188-8","article-title":"Identification of cryptolepine metabolites in rat and human hepatocytes and metabolism and pharmacokinetics of cryptolepine in Sprague Dawley rats","volume":"18","author":"AD Forkuo","year":"2017","journal-title":"BMC Pharmacol Toxicol"},{"issue":"1","key":"pntd.0008489.ref027","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1186\/s12936-018-2283-8","article-title":"Isobolographic analysis of co-administration of two plant-derived antiplasmodial drug candidates, cryptolepine and xylopic acid, in Plasmodium berghei","volume":"17","author":"EO Ameyaw","year":"2018","journal-title":"Malaria J"},{"key":"pntd.0008489.ref028","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/S0163-7258(03)00071-8","article-title":"Potential chemotherapeutic targets in the purine metabolism of parasites","volume":"99","author":"MH El Kouni","year":"2003","journal-title":"Pharmacol Therap"},{"issue":"7","key":"pntd.0008489.ref029","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1084\/jem.20151519","article-title":"Radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin-like quinolone and atovaquone","volume":"213","author":"LA Lawres","year":"2016","journal-title":"The J Exper Med"},{"issue":"5","key":"pntd.0008489.ref030","doi-asserted-by":"crossref","first-page":"e0007030","DOI":"10.1371\/journal.pntd.0007030","article-title":"The effects of trans-chalcone and chalcone 4 hydrate on the growth of Babesia and Theileria","volume":"13","author":"GE-S Batiha","year":"2019d","journal-title":"PLoS Negl Trop Dis"},{"issue":"2","key":"pntd.0008489.ref031","doi-asserted-by":"crossref","first-page":"e0228996","DOI":"10.1371\/journal.pone.0228996","article-title":"Safety and efficacy of hydroxyurea and eflornithine against most blood parasites Babesia and Theileria","volume":"15","author":"GE-S Batiha","year":"2020c","journal-title":"PLoS ONE"},{"key":"pntd.0008489.ref032","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1186\/s13071-019-3520-x","article-title":"Ellagic acid microspheres restrict the growth of Babesia and Theileria in vitro and Babesia microti in vivo","volume":"12","author":"AM Beshbishy","year":"2019a","journal-title":"Parasite Vectors"},{"key":"pntd.0008489.ref033","doi-asserted-by":"crossref","first-page":"425","DOI":"10.4103\/1995-7645.267586","article-title":"Inhibitory effects of methanolic Olea europaea and acetonic Acacia laeta on growth of Babesia and Theileria","volume":"12","author":"AM Beshbishy","year":"2019b","journal-title":"Asian Pac J Trop Med"},{"key":"pntd.0008489.ref034","first-page":"8","article-title":"Anti-piroplasmic potential of the methanolic Peganum harmala seeds and ethanolic Artemisia absinthium leaf extracts","volume":"29","author":"GE-S Batiha","year":"2019a","journal-title":"J Protoz Res"},{"key":"pntd.0008489.ref035","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.ttbdis.2019.04.016","article-title":"Inhibitory effects of Syzygium aromaticum and Camellia sinensis methanolic extracts on the growth of Babesia and Theileria parasites","volume":"10","author":"GE-S Batiha","year":"2019b","journal-title":"Tick Tick Borne Dis"},{"key":"pntd.0008489.ref036","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s41182-019-0171-8","article-title":"Evaluation of the inhibitory effect of ivermectin on the growth of Babesia and Theileria parasites in vitro and in vivo","volume":"47","author":"GE-S Batiha","year":"2019c","journal-title":"Trop Med Health"},{"key":"pntd.0008489.ref037","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1124\/pr.58.3.10","article-title":"Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies","volume":"58","author":"TC Chou","year":"2006","journal-title":"Pharmacol Rev"}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0008489","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,27]],"date-time":"2020-08-27T17:26:58Z","timestamp":1598549218000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0008489"}},"subtitle":[],"editor":[{"given":"Photini","family":"Sinnis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,8,27]]},"references-count":37,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8,27]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0008489","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,27]]}}}