In vitro screening of compounds from the Food and Drug Administration-approved library identifies anti-Babesia gibsoni activity of idarubicin hydrochloride and vorinostat |
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| Institution: | 1. National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan;2. College of Veterinary Medicine and Biomedical Sciences, Cavite State University, Indang, Cavite, Philippines;3. Biotechnology Department, Animal Health Research Institute, Dokki, Egypt;4. School of Basic Medicine, Hubei University of Arts and Science, Xiangyang 441053, China;1. Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu, São Paulo, Brazil;2. Faculdades Integradas de Bauru- FIB, Bauru, São Paulo, Brazil;1. Australian National Phenome Centre, Health Futures Institute, Murdoch University, Harry Perkins Building, Perth, Western Australia 6150, Australia;2. College of Science, Health, Engineering and Education, Murdoch University, Murdoch, Western Australia 6150, Australia;3. Institute of Cash Crops, Hebei Academy of Agriculture and Forestry Sciences, Shijiazhuang 050051, China;4. Departamento de Biologia Animal, Instituto de Ciências Biológicas e da Saúde, Universidade Federal Rural do Rio de Janeiro, BR-465 km 7, Seropédica, RJ 23897-000, Brazil;1. Núcleo de Reabilitação da Fauna Silvestre e Centro de Triagem de Animais Silvestres (NURFS/CETAS/UFPEL), Universidade Federal de Pelotas (UFPel), Campus Universitário s/n, CEP 96160-000 Capão do Leão, RS, Brazil;2. Laboratório de Parasitologia de Animais Silvestres (LAPASIL), Departamento de Microbiologia e Parasitologia, Instituto de Biologia, Universidade Federal de Pelotas (UFPel), Campus Universitário s/n, CEP 96160-000 Capão do Leão, RS, Brazil;3. Programa de Pós-Graduação em Educação, Faculdade de Educação, Universidade Federal de Pelotas, Rua Alberto Rosa, 154, CEP 96010-770 Pelotas, RS, Brazil;4. Programa de Pós-Graduação em Biodiversidade Animal, Departamento de Ecologia, Zoologia e Genética, Instituto de Biologia, Universidade Federal de Pelotas (UFPel), Campus Universitário s/n, CEP 96160-00 Capão do Leão, RS, Brazil;5. Napeia consultoria e projetos Ltda, Av. Júlio de Castilhos, 2773, CEP 95010-003 Caxias do Sul, RS, Brazil;6. Grupo especial de proteção do ambiente aquático do Rio Grande do Sul (GEEPAA –RS), CEP 96010-900 Pelotas, RS, Brazil;1. Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Tai''an, China;2. China Animal Health and Epidemiology Center, Qing''dao, China;3. Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai''an, China;4. Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Tai''an, China |
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| Abstract: | Babesia gibsoni is mainly transmitted by hard ticks of the genus Rhipicephalus (R. sanguineus) and Haemaphysalis (H. longicornis), and causes canine babesiosis. Clinical manifestations of B. gibsoni infection include fever, hemoglobinemia, hemoglobinuria, and progressive anemia. Traditional antibabesial therapy, such as imidocarb dipropionate or diminazene aceturate, can only alleviate severe clinical manifestations and cannot eliminate parasites in the host. Food and Drug Administration (FDA)-approved drugs are a solid starting point for researching novel therapy strategies for canine babesiosis. In this work, we screened 640 FDA-approved drugs against the growth of B. gibsoni in vitro. Among them, 13 compounds (at 10 μM) exhibited high growth inhibition (>60%), and two compounds, namely idarubicin hydrochloride (idamycin) and vorinostat, were chosen for further investigation. The half-maximal inhibitory concentration (IC50) values of idamycin and vorinostat were determined to be 0.044 ± 0.008 μM and 0.591 ± 0.107 μM, respectively. Viability results indicated that a concentration of 4 × IC50 of vorinostat prevented the regrowth of treated B. gibsoni, whereas parasites treated with 4 × IC50 concentration of idamycin remained viable. The B. gibsoni parasites treated with vorinostat exhibited degeneration within erythrocytes and merozoites, in contrast to the oval or signet-ring shape of normal B. gibsoni parasites. In conclusion, FDA-approved drugs offer a valuable platform for drug repositioning in antibabesiosis research. Particularly, vorinostat demonstrated promising inhibitory effects against B. gibsoni in vitro, and further studies on vorinostat are necessary to elucidate its mechanism as a novel treatment in infected animal models. |
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