caa a22 4500 445339861 CHVBK 20180317142808.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s00436-011-2427-z doi (NATIONALLICENCE)springer-10.1007/s00436-011-2427-z Synergy of the antiretroviral protease inhibitor indinavir and chloroquine against malaria parasites in vitro and in vivo [Elektronische Daten] [Xiaofen Li, Zhengxiang He, Lili Chen, Yayong Li, Qinyan Li, Siting Zhao, Zhu Tao, Wen Hu, Li Qin, Xiaoping Chen] Many malaria-endemic areas are also associated with high rates of human immunodeficiency virus (HIV) infection. An understanding of the chemotherapeutic interactions that occur during malaria and HIV co-infections is important. Our previous studies have demonstrated that some antiretroviral protease inhibitors are effective in inhibiting Plasmodium falciparum growth in vitro. Currently, studies examining the interactions between antiretroviral protease inhibitors and antimalarial drugs are being conducted, but the data are limited. In this study, we examined the synergistic interactions between the antiretroviral protease inhibitor indinavir and chloroquine (CQ) in chloroquine-resistant and chloroquine-sensitive malaria parasites in vitro and in vivo. In vitro, by using modified fixed-ratio isobologram method, fractional inhibitory concentrations index (FICI) was calculated to indicate the interaction between the two drugs. The results demonstrated that indinavir interacted synergistically with chloroquine against both chloroquine-sensitive P. falciparum clone 3D7 (mean FICI 0.784) and multidrug-resistant P. falciparum clone Dd2 (mean FICI 0.599). In vivo drug interactions were measured using a 4-day suppressive test in a rodent malaria model infected with Plasmodium chabaudi. We observed that indinavir enhanced the antimalarial activity of chloroquine against both the chloroquine-sensitive line P. chabaudi ASS and the chloroquine-resistant line P. chabaudi ASCQ. More importantly, chloroquine had a 100% clearance of asexual parasites when used in combination with indinavir at an appropriate dose ratio (10mg/kg CQ + 1.8g/kg indinavir) where there was no obvious toxicity. We conclude from this study that the combination of indinavir and chloroquine may become a novel antimalarial drug regimen. Springer-Verlag, 2011 Li Xiaofen Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, 510530, Guangzhou, China aut He Zhengxiang Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, 510530, Guangzhou, China aut Chen Lili Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, 510530, Guangzhou, China aut Li Yayong Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, 510530, Guangzhou, China aut Li Qinyan Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, 510530, Guangzhou, China aut Zhao Siting Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, 510530, Guangzhou, China aut Tao Zhu Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, 510530, Guangzhou, China aut Hu Wen Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, 510530, Guangzhou, China aut Qin Li Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, 510530, Guangzhou, China aut Chen Xiaoping Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, 510530, Guangzhou, China aut Parasitology Research Springer-Verlag 109/6(2011-12-01), 1519-1524 0932-0113 109:6<1519 2011 109 436 https://doi.org/10.1007/s00436-011-2427-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00436-011-2427-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Li Xiaofen Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, 510530, Guangzhou, China aut NATIONALLICENCE 700 1- He Zhengxiang Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, 510530, Guangzhou, China aut NATIONALLICENCE 700 1- Chen Lili Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, 510530, Guangzhou, China aut NATIONALLICENCE 700 1- Li Yayong Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, 510530, Guangzhou, China aut NATIONALLICENCE 700 1- Li Qinyan Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, 510530, Guangzhou, China aut NATIONALLICENCE 700 1- Zhao Siting Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, 510530, Guangzhou, China aut NATIONALLICENCE 700 1- Tao Zhu Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, 510530, Guangzhou, China aut NATIONALLICENCE 700 1- Hu Wen Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, 510530, Guangzhou, China aut NATIONALLICENCE 700 1- Qin Li Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, 510530, Guangzhou, China aut NATIONALLICENCE 700 1- Chen Xiaoping Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, 510530, Guangzhou, China aut NATIONALLICENCE 773 0- Parasitology Research Springer-Verlag 109/6(2011-12-01), 1519-1524 0932-0113 109:6<1519 2011 109 436 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer