{"doi":"10.1111/j.1550-7408.1992.tb04856.x","title":"<i>Plasmodium falciparum</i>: Differential Sensitivity In Vitro to E‐64 (Cysteine Protease Inhibitor) and Pepstatin A (Aspartyl Protease Inhibitor)","abstract":"<jats:p><jats:bold>ABSTRACT</jats:bold> We investigated the effect of a cysteine proteinase inhibitor (E‐64) and an aspartyl proteinase inhibitor (Pepstatin A) on asexual erythrocytic stages of <jats:italic>Plasmodium falciparum</jats:italic> in culture. These two protease inhibitors showed different patterns of activity. E‐64 acted preferentially against trophozoite and schizont stages. After 48 h incubation at high concentrations of E‐64 (28, 140, 280 μM), growth was totally abolished and the parasites presented characteristic enlarged food vacuoles. Morphological alterations were also seen after shorter incubation periods (6 h at 28 μM) or 12 h at the inhibitory concentration 50% (12 μM), but an additional culture period (24 h) in inhibitor‐free medium allowed normal parasite development, demonstrating a parasitostatic effect. E‐64 acts on parasite multiplication; the normal merozoite maturation was altered and the normal reinvasion process partially impaired. Pepstatin A used at the inhibitory concentration 50% (4 μM) killed the parasites before trophozoite development and had a major effect on schizonts maturation. No altered parasite development occurred during an additional culture period without Pepstatin A, demonstrating a parasiticidal effect. E‐64 and Pepstatin A used in combination inhibit the parasite growth with a strong synergistic effect.</jats:p>","journal":"The Journal of Protozoology","year":1992,"id":18452,"datarank":6.247201180392734,"base_score":4.499809670330265,"endowment":4.499809670330265,"self_citation_contribution":0.6749714505495399,"citation_network_contribution":5.572229729843194,"self_endowment_contribution":0.6749714505495399,"citer_contribution":5.572229729843194,"corpus_percentile":null,"corpus_rank":null,"citation_count":89,"citer_count":89,"citers_with_citation_signal":82,"citers_with_endowment":82,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":128206,"name":"RONAN JAMBOU","orcid":null,"position":1,"is_corresponding":false},{"id":128207,"name":"JEAN SAVEL","orcid":null,"position":2,"is_corresponding":false},{"id":128208,"name":"GINETTE JAUREGUIBERRY","orcid":null,"position":3,"is_corresponding":false},{"id":128205,"name":"ERIC BAILLY","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.499809670330265,"endowment":4.499809670330265,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"1522541","pmcid":null,"openalex_id":"https://openalex.org/W2063684273","authors":[],"funders":[],"total_grants":0,"fwci":2.0607,"citation_percentile":0.87129968,"influential_citations":5,"citation_trend":[{"year":2012,"count":3},{"year":2013,"count":3},{"year":2014,"count":3},{"year":2015,"count":3},{"year":2016,"count":2},{"year":2017,"count":2},{"year":2018,"count":2},{"year":2019,"count":1},{"year":2020,"count":1},{"year":2022,"count":1},{"year":2023,"count":2},{"year":2024,"count":3},{"year":2025,"count":3}],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1550-7408.1992.tb04856.x","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1550-7408.1992.tb04856.x","host_type":"publisher"},{"url":"https://doi.org/10.1111/j.1550-7408.1992.tb04856.x","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/1522541","host_type":"repository"}],"fields_of_study":["Malaria Research and Control","Drug Transport and Resistance Mechanisms","Parasites and Host Interactions","Biology","Medicine","Animals","Antimalarials","Aspartic Acid Endopeptidases","Cells, Cultured","Cysteine Proteinase Inhibitors","Drug Interactions","Leucine","Pepstatins","Plasmodium falciparum"],"mesh_terms":["Animals","Antimalarials","Cells, Cultured","Drug Interactions","Leucine","Pepstatins","Plasmodium falciparum","Cysteine Proteinase Inhibitors","Aspartic Acid Endopeptidases"],"keywords":["Pepstatin","Plasmodium falciparum","Cysteine protease","Protease inhibitor (pharmacology)","In vitro","Protease","Chemistry","Biochemistry","Enzyme","Biology","Virology","Malaria","Human immunodeficiency virus (HIV)","Immunology"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Zero hunger"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-03T22:05:50.056393Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}