Synthesis and biological activity of new potential antimalarial: 1H-pyrazolo[3,4-b]pyridine derivatives.
The appearance of drug resistant Plasmodium falciparum malaria necessitates the search for novel antimalarial agents. Using the classical ring-bioisosterism concept as a strategy to develop new potential drugs, 1H-pyrazolo[3,4-b]pyridine 4-aminomethanol compounds were designed and synthesized as isosteres of the classical quinoline antimalarial mefloquine. The hydrochloride form of these compounds were tested for in vitro antimalarial activity against chloroquine-sensitive (Sierra Leone D-6) and resistant (Indochina W-2) clones of P. falciparum. The results described herein indicated that 1-H-pyrazolo[3,4-b]pyridine system represents a bioisosteric framework to quinoline system in the antimalarial activity.
Dias
L R
LR
Instituto de Química, Univ. Federal do Rio de Janeiro, Cidade Universitária, RJ, Brazil.
Freitas
A C
AC
Barreiro
E J
EJ
Goins
D K
DK
Nanayakkara
D
D
McChesney
J D
JD
Dias
R S
RS
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D002522:Chlorocebus aethiops; D002738:Chloroquine / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects*; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D014709:Vero Cells
D000962:Antimalarials; D011725:Pyridines; D002738:Chloroquine