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| Content Provider | frontiers |
|---|---|
| Author | El Bissati, Kamal Redel, Henry Ting, Li-Min Lykins, Joseph D. McPhillie, Martin J. Upadhya, Rajendra Woster, Patrick M. Yarlett, Nigel Kim, Kami Weiss, Louis M. |
| Abstract | Twenty-two compounds belonging to several classes of polyamine analogs have been examined for their ability to inhibit the growth of the human malaria parasite Plasmodium falciparum in vitro and in vivo. Four lead compounds from the thiourea sub-series and one compound from the urea-based analogs were found to be potent inhibitors of both chloroquine-resistant (Dd2) and chloroquine-sensitive (3D7) strains of Plasmodium with IC50 values ranging from 150 to 460 nM. In addition, the compound RHW, N1,N7-bis (3-(cyclohexylmethylamino) propyl) heptane-1,7-diamine tetrabromide was found to inhibit Dd2 with an IC50 of 200 nM. When RHW was administered to P. yoelii-infected mice at 35 mg/kg for 4 days, it significantly reduced parasitemia. RHW was also assayed in combination with the ornithine decarboxylase inhibitor difluoromethylornithine, and the two drugs were found not to have synergistic antimalarial activity. Furthermore, these inhibitors led to decreased cellular spermidine and spermine levels in P. falciparum, suggesting that they exert their antimalarial activities by inhibition of spermidine synthase. |
| ISSN | 22352988 |
| DOI | 10.3389/fcimb.2019.00009 |
| Volume Number | 9 |
| Journal | Frontiers in Cellular and Infection Microbiology |
| Language | English |
| Publisher Date | 2019-02-14 |
| Access Restriction | Open |
| Subject Keyword | Spermine Spermidine Synthase Polyamine Malaria Thiourea Plasmodium |
| Content Type | Text |
| Resource Type | Article |
| Subject | Infectious Diseases Immunology Microbiology Microbiology (medical) |
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