scholarly journals Microwave-assisted synthesis of C-8 aryl and heteroaryl inosines and determination of their inhibitory activities against Plasmodium falciparum purine nucleoside phosphorylase

2014 ◽  
Vol 82 ◽  
pp. 459-465 ◽  
Author(s):  
Alba Gigante ◽  
Eva-María Priego ◽  
Paula Sánchez-Carrasco ◽  
Luis Miguel Ruiz-Pérez ◽  
Johan Vande Voorde ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Purine Nucleoside Phosphorylase ◽  
Purine Nucleoside ◽  
Microwave Assisted Synthesis ◽  
Nucleoside Phosphorylase ◽  
Microwave Assisted ◽  
Inhibitory Activities

Exploring new inhibitors of Plasmodium falciparum purine nucleoside phosphorylase

2010 ◽  
Vol 45 (11) ◽  
pp. 5140-5149 ◽  
Author(s):  
Huaqing Cui ◽  
Gian Filippo Ruda ◽  
Juana Carrero-Lérida ◽  
Luis M. Ruiz-Pérez ◽  
Ian H. Gilbert ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Purine Nucleoside Phosphorylase ◽  
Purine Nucleoside ◽  
Nucleoside Phosphorylase

Identification of a novel putative inhibitor of the Plasmodium falciparum purine nucleoside phosphorylase: exploring the purine salvage pathway to design new antimalarial drugs

2017 ◽  
Vol 21 (3) ◽  
pp. 677-695 ◽  
Author(s):  
Luciano Porto Kagami ◽  
Gustavo Machado das Neves ◽  
Ricardo Pereira Rodrigues ◽  
Vinicius Barreto da Silva ◽  
Vera Lucia Eifler-Lima ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Purine Nucleoside Phosphorylase ◽  
Antimalarial Drugs ◽  
Purine Nucleoside ◽  
Salvage Pathway ◽  
Purine Salvage ◽  
Nucleoside Phosphorylase

scholarly journals Genetic resistance to purine nucleoside phosphorylase inhibition in Plasmodium falciparum

2018 ◽  
Vol 115 (9) ◽  
pp. 2114-2119 ◽  
Author(s):  
Rodrigo G. Ducati ◽  
Hilda A. Namanja-Magliano ◽  
Rajesh K. Harijan ◽  
J. Eduardo Fajardo ◽  
Andras Fiser ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Transition State ◽  
Gene Amplification ◽  
Purine Nucleoside Phosphorylase ◽  
Point Mutations ◽  
Catalytic Site ◽  
Purine Nucleoside ◽  
Drug Pressure ◽  
Nucleoside Phosphorylase ◽  
Transition State Analog

Plasmodium falciparum causes the most lethal form of human malaria and is a global health concern. The parasite responds to antimalarial therapies by developing drug resistance. The continuous development of new antimalarials with novel mechanisms of action is a priority for drug combination therapies. The use of transition-state analog inhibitors to block essential steps in purine salvage has been proposed as a new antimalarial approach. Mutations that reduce transition-state analog binding are also expected to reduce the essential catalytic function of the target. We have previously reported that inhibition of host and P. falciparum purine nucleoside phosphorylase (PfPNP) by DADMe-Immucillin-G (DADMe-ImmG) causes purine starvation and parasite death in vitro and in primate infection models. P. falciparum cultured under incremental DADMe-ImmG drug pressure initially exhibited increased PfPNP gene copy number and protein expression. At increased drug pressure, additional PfPNP gene copies appeared with point mutations at catalytic site residues involved in drug binding. Mutant PfPNPs from resistant clones demonstrated reduced affinity for DADMe-ImmG, but also reduced catalytic efficiency. The catalytic defects were partially overcome by gene amplification in the region expressing PfPNP. Crystal structures of native and mutated PfPNPs demonstrate altered catalytic site contacts to DADMe-ImmG. Both point mutations and gene amplification are required to overcome purine starvation induced by DADMe-ImmG. Resistance developed slowly, over 136 generations (2136 clonal selection). Transition-state analog inhibitors against PfPNP are slow to induce resistance and may have promise in malaria therapy.

Identification of a peptide derived from a Bothrops moojeni metalloprotease with in vitro inhibitory action on the Plasmodium falciparum purine nucleoside phosphorylase enzyme (PfPNP)

Biochimie ◽  
2019 ◽  
Vol 162 ◽  
pp. 97-106
Author(s):  
Gracianny Gomes Martins ◽  
Rudson de Jesus Holanda ◽  
Jorge Alfonso ◽  
Ana Fidelina Gómez Garay ◽  
Ana Paula de Azevedo dos Santos ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Inhibitory Action ◽  
Purine Nucleoside Phosphorylase ◽  
Purine Nucleoside ◽  
Nucleoside Phosphorylase ◽  
Bothrops Moojeni
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