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Leishmania donovani: oral therapy with glycosyl 1,4-dihydropyridine analogue showing apoptosis like phenotypes targeting pteridine reductase 1 in intracellular amastigotes.

Jaspreet Kaur, Nasib Singh, Biswajit Kumar Singh, Anuradha Dube, Rama Pati Tripathi, Prashant Singh, Neeloo Singh

Drug Target Discovery and Development Division, Central Drug Research Institute, Chattar Manzil Palace, CSIR, Lucknow, India.

Journal Article: Experimental Parasitology (impact factor: 1.6). 02/2010; 125(3):310-4. DOI: 10.1016/j.exppara.2010.02.011

Abstract

Glycosyl 1,4-dihydropyridine analogue (2,6-dimethyl-4-(3-O-benzyl-1,2-O-isopropylidene-beta-l-threo pentofuranos-4-yl)-1-phenyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid diethyl ester) synthesized in our laboratory, inhibited Leishmania donovani infection in vitro and in hamsters (Mesocricetus auratus) when administered orally. This analogue is nontoxic, cell-permeable and orally effective. This glycosyl dihydropyridine analogue functioned through arrest of cells in sub-G0/G1-phase, triggering mitochondrial membrane depolarization-mediated programmed cell death of the intracellular amastigotes.

Source: PubMed

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Keywords

2,6-dimethyl-4-(3-O-benzyl-1,2-O-isopropylidene-beta-l-threo pentofuranos-4-yl)-1-phenyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid diethyl ester
 
cell-permeable
 
Glycosyl 1,4-dihydropyridine analogue
 
glycosyl dihydropyridine analogue functioned
 
inhibited Leishmania donovani infection
 
intracellular amastigotes
 
Mesocricetus auratus
 
mitochondrial membrane depolarization-mediated