Leishmania donovani: oral therapy with glycosyl 1,4-dihydropyridine analogue showing apoptosis like phenotypes targeting pteridine reductase 1 in intracellular amastigotes.
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.
Kaur
Jaspreet
J
Drug Target Discovery and Development Division, Central Drug Research Institute, Chattar Manzil Palace, CSIR, Lucknow, India.
Singh
Nasib
N
Singh
Biswajit Kumar
BK
Dube
Anuradha
A
Tripathi
Rama Pati
RP
Singh
Prashant
P
Singh
Neeloo
N
D000284:Administration, Oral; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005434:Flow Cytometry; D006027:Glycosides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008264:Macrophages / Q000469:parasitology*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D010088:Oxidoreductases / Q000187:drug effects*; D010641:Phenotype; D013154:Spleen / Q000469:parasitology
C543591:2,6-dimethyl-4-(3-O-benzyl-1,2-O-isopropylidene-beta-L-threo-pentofuranos-4-y)-1-phenyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid diethyl ester; D000981:Antiprotozoal Agents; D004095:Dihydropyridines; D006027:Glycosides; D010088:Oxidoreductases; C085592:pteridine reductase