Synthesis and antimalarial evaluation of 1, 3, 5-trisubstituted pyrazolines.
A series of 1,3,5-trisubstituted pyrazolines were synthesized and evaluated for in vitro antimalarial efficacy against chloroquine sensitive (MRC-02) as well as chloroquine resistant (RKL9) strains of Plasmodium falciparum. The activity was at nano molar concentration. beta-hematin formation inhibition activity (BHIA(50)) of the pyrazolines were determined and correlated with antimalarial activity. A reasonably good correlation (r=0.62) was observed between antimalarial activity (IC(50)) and BHIA(50). This suggests that antimalarial mode of action of this class of compounds appears to be similar to that of chloroquine and involves the inhibition of hemozoin formation. Some of the compounds were showing better antimalarial activity than chloroquine against resistant strain of P. falciparum and were also found active in the in vivo experiment.
Acharya
Badri Narayan
BN
Defence Research & Development Establishment, Jhansi Road, Gwalior 474002, India.
Saraswat
Deepika
D
Tiwari
Mugdha
M
Shrivastava
Asish Kumar
AK
Ghorpade
Ramarao
R
Bapna
Saroj
S
Kaushik
Mahabir Parshad
MP
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance; D006367:HeLa Cells; D006427:Hemin / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D010962:Plasmodium berghei / Q000187:drug effects / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects / Q000378:metabolism; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity
D000962:Antimalarials; D011720:Pyrazoles; D006427:Hemin; D002738:Chloroquine