Synthesis and comparison of antimalarial activity of febrifugine derivatives including halofuginone.
Febrifugine and its derivatives including halofuginone which possess very high activity against malaria were prepared synthetically from easily available starting material, 3-hydroxy picoline, and using simple reaction conditions. Synthesis of 2-amino-5, 6-methylenedioxy benzoic acid, (which is an intermediate for the process) is described. The selectivity enhancement in nitration of 3, 4-methylenedioxybenzaldehyde towards 6-nitro isomer was done with the help of surfactant. The antimalarial activity of synthesized compounds was determined by using in vitro assays against chloroquine sensitive (D6), chloroquine resistant (W2) Plasmodium falciparum strains for susceptibility and two mammalian cell lines (neuronal cell line NG108 and macrophage cell line J774) for cytotoxicity. The IC(50)s of halofuginone was observed to be the best among the synthesized derivatives of febrifugine.
1Chemical Engineering Division, Institute of Chemical Technology, University of Mumbai, Matunga, Mumbai, India. bhupesh.samant@gmail.com
Bhupesh S
BS
Samant
Mugdha G
MG
Sukhthankar
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001565:Benzoates / Q000138:chemical synthesis; D002460:Cell Line; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D052999:Quinazolinones / Q000138:chemical synthesis* / Q000494:pharmacology*
D000962:Antimalarials; D001565:Benzoates; D010880:Piperidines; D011799:Quinazolines; D052999:Quinazolinones; C001207:febrifugine; C010176:halofuginone