Synthesis and antifilarial evaluation of N1,Nn- xylofuranosylated diaminoalkanes.
A series of N(1),N(n)-xylofuranosylated diaminoalkanes (3-9 and 11-18) has been synthesized either by reductive amination of deoxy xylouloses (2a, 2b) with amines followed by one pot reduction with NaBH(4) or NaCNBH(3); or by 1,4-conjugate addition of amines to glycosyl olefinic esters (10a, 10b). The compounds were screened for their interference with filarial worms' glutathione metabolism, a potential target for chemotherapeutic attack. Interestingly, these compounds affected intracellular glutathione, gamma-glutamyl cysteine synthetase, glutathione reductase and glutathione-S-transferase(s) of bovine filarial worms to varying degrees. Some of the compounds though effected the motility and MTT reduction potential of filarial worms Brugia malayi, however, little microfilaricidal and macrofilaricidal were noted with compounds at 50mg/kg oral dose. Compounds 6, 16 and 17 were evaluated also for in vivo activity.
Tiwari
V K
VK
Division of Medicinal Chemistry, Central Drug Research Institute, Lucknow-226001, India.
Tewari
N
N
Katiyar
D
D
Tripathi
R P
RP
Arora
K
K
Gupta
S
S
Ahmad
R
R
Srivastava
A K
AK
Khan
M A
MA
Murthy
P K
PK
Walter
R D
RD
D000473:Alkanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000977:Antiparasitic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017178:Brugia malayi / Q000187:drug effects; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002330:Carmustine / Q000494:pharmacology; D002417:Cattle; D003959:Diamines / Q000737:chemistry* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005370:Filarioidea / Q000187:drug effects* / Q000201:enzymology; D005721:Glutamate-Cysteine Ligase / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D005982:Glutathione Transferase / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008842:Microfilariae / Q000187:drug effects / Q000378:metabolism; D012377:Rodentia / Q000469:parasitology; D024483:Vitamin K 3 / Q000494:pharmacology; D014994:Xylose / Q000031:analogs & derivatives*
D000473:Alkanes; D000977:Antiparasitic Agents; D003959:Diamines; D004791:Enzyme Inhibitors; D019328:Buthionine Sulfoximine; D024483:Vitamin K 3; D014994:Xylose; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D002330:Carmustine