5 documents found, page 1 of 1
A novel 4-aminoquinoline chemotype with multistage antimalarial activity and la...
Ferreira, Letícia Tiburcio; Cassiano, Gustavo Capatti; Alvarez, Luis Carlos Salazar; Okombo, John; Calit, Juliana; Fontinha, Diana; Gil-Iturbe, EvaArtemisinin-based combination therapy (ACT) is the mainstay of effective treatment of Plasmodium falciparum malaria. However, the long-term utility of ACTs is imperiled by widespread partial artemisinin resistance in Southeast Asia and its recent emergence in parts of East Africa. This underscores the need to identify chemotypes with new modes of action (MoAs) to circumvent resistance to ACTs. In this study, we...
Expansion of a Specific Plasmodium falciparum PfMDR1 Haplotype in Southeast Asi...
Calçada, Carla; Silva, Miguel; Baptista, Vitória; Thathy, Vandana; Silva-Pedrosa, Rita; Granja, Diana; Ferreira, Pedro Eduardo; Gil, José PedroArtemisinin-based combination therapies (ACTs) have been vital in reducing malaria mortality rates since the 2000s. Their efficacy, however, is threatened by the emergence and spread of artemisinin resistance in Southeast Asia. The Plasmodium falciparum multidrug resistance protein 1 (PfMDR1) transporter plays a central role in parasite resistance to ACT partner drugs through gene copy number variations (CNV) a...
Expansion of a specific plasmodium falciparum PfMDR1 Haplotype in southeast Asi...
Calçada, Carla Sofia Martins; Silva, Miguel; Baptista, Vitória; Thathy, Vandana; Pedrosa, Ana; Granja, Diana; Ferreira, Pedro Eduardo; Gil, José PedroArtemisinin-based combination therapies (ACTs) have been vital in reducing malaria mortality rates since the 2000s. Their efficacy, however, is threatened by the emergence and spread of artemisinin resistance in Southeast Asia. The Plasmodium falciparum multidrug resistance protein 1 (PfMDR1) transporter plays a central role in parasite resistance to ACT partner drugs through gene copy number variations (CNV) a...
Globally prevalent PfMDR1 mutations modulate Plasmodium falciparum susceptibili...
Veiga, Maria Isabel Mendes; Dhingra, Satish K.; Henrich, Philipp P.; Straimer, Judith; Gnädig, Nina; Uhlemann, Anne-Catrin; Martin, Rowena E.Antimalarial chemotherapy, globally reliant on artemisinin-based combination therapies (ACTs), is threatened by the spread of drug resistance in Plasmodium falciparum parasites. Here we use zinc-finger nucleases to genetically modify the multidrug resistance-1 transporter PfMDR1 at amino acids 86 and 184, and demonstrate that the widely prevalent N86Y mutation augments resistance to the ACT partner drug amodiaq...
In vivo selection of plasmodium falciparum parasites carrying the chloroquine-s...
Sisowath, Christin; Petersen, Ines; Veiga, Maria Isabel; Martensson, Andreas; Premji, Zul; Bjorkman, Anders; Fidock, David A.; Gil, José PedroBackground. Artemether-lumefantrine (AL) is a major and highly effective artemisinin-based combination therapy that is becoming increasingly important as a new first-line therapy against Plasmodium falciparum malaria. However, recrudescences occurring after AL treatment have been reported. Identification of drug-specific parasite determinants that contribute to treatment failures will provide important tools fo...