Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The malaria parasite Plasmodium falciparum degrades hemoglobin in its acidic food vacuole for use as a major nutrient source. A novel metallopeptidase activity, falcilysin, was purified from food vacuoles and characterized. Falcilysin appears to function downstream of the aspartic proteases plasmepsins I and II and the cysteine protease falcipain in the hemoglobin proteolytic pathway. It is unable to cleave hemoglobin or denatured globin but readily destroys peptide fragments of hemoglobin. Falcilysin cleavage sites along the alpha and beta chains of hemoglobin are polar in character, with charged residues located in the P1 and/or P4' positions. In contrast, plasmepsins I and II and falcipain prefer hydrophobic residues around the scissile bond. The gene encoding falcilysin has been cloned. Its coding sequence exhibits features characteristic of clan ME family M16 metallopeptidases, including an "inverted" HXXEH active site motif. Falcilysin shares primary structural features with M16 family members such as insulysin, mitochondrial processing peptidase, nardilysin, and pitrilysin as well as with data base hypothetical proteins that are potential M16 family members. The characterization of falcilysin increases our understanding of hemoglobin catabolism in P. falciparum and the unusual M16 family of metallopeptidases.
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PMID:Identification and characterization of falcilysin, a metallopeptidase involved in hemoglobin catabolism within the malaria parasite Plasmodium falciparum. 1054 84

In this paper, the design, synthesis and biological evaluation of a set of quinazoline-2,4,6-triamine derivatives (1-9) as trypanocidal, antileishmanial and antiplasmodial agents are explained. The compounds were rationalized basing on docking studies of the dihydrofolate reductase (DHFR from Trypanosoma cruzi, Leishmania major and Plasmodium vivax) and pteridin reductase (PTR from T. cruzi and L. major) structures. All compounds were in vitro screened against both bloodstream trypomastigotes of T. cruzi (NINOA and INC-5 strains) and promatigotes of Leishmania mexicana (MHOM/BZ/61/M379 strain), and also for cytotoxicity using Vero cell line. Against T. cruzi, three compounds (5, 6 and 8) were the most effective showing a better activity profile than nifurtimox and benznidazole (reference drugs). Against L. mexicana, four compounds (5, 6, 8, and 9) exhibited the highest activity, even than glucantime (reference drug). In the cytotoxicity assay, protozoa were more susceptible than Vero cells. In vivo Plasmodium berghei assay (ANKA strain), the compounds 1, 5, 6 and 8 showed a more comparable activity than chloroquine and pyrimethamine (reference drugs) when they were administrated by the oral route. The antiprotozoal activity of these substances, endowed with redox properties, represented a good starting point for a medicinal chemistry program aiming for chemotherapy of Chagas' disease, leishmaniosis and malaria.
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PMID:Design, synthesis and biological evaluation of quinazoline derivatives as anti-trypanosomatid and anti-plasmodial agents. 2589 34

The discovery that Volatile Organic Compounds (VOCs) can be biomarkers for several diseases has led to the conception of their possible application as diagnostic tools. In this study, we aimed at defining of diagnostic signatures for the presence of malaria transmissible stages in infected individuals. To do this, we compared VOCs released by asexual and sexual stage cultures of Plasmodium falciparum, the deadliest species of malaria, with those emitted by uninfected red blood cells (RBCs). VOC analysis was carried out with an innovative set-up, where each sample was simultaneously analysed by proton transfer reaction time of flight mass spectrometry (PTR-ToF-MS) and an electronic nose. PTR-Tof-MS results show that sexual stages are characterized by a larger emission of hexanal, compared with uninfected or asexual stage-infected RBCs, which makes them clearly identifiable. PTR-Tof-MS analysis also detected differences in VOC composition between asexual stages and uninfected RBCs. These results have been substantially replicated by the electronic nose analysis and may open the possibility to develop sensitive and easy-to-use devices able to detect sexual parasite stages in infected individuals. This study also demonstrates that the combination of mass spectrometry with electronic noses is a useful tool to identify markers of diseases and to support the development of optimized sensors.
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PMID:Simultaneous Proton Transfer Reaction-Mass Spectrometry and electronic nose study of the volatile compounds released by Plasmodium falciparum infected red blood cells in vitro. 3145 7