TY - JOUR
T1 - Carbon isosteres of the 4-aminopyridine substructure of chloroquine
T2 - Effects on pKa, hematin binding, inhibition of hemozoin formation, and parasite growth
AU - Cheruku, Srinivasa R.
AU - Maiti, Souvik
AU - Dorn, Arnulf
AU - Scorneaux, Bernard
AU - Bhattacharjee, Apurba K.
AU - Ellis, William Y.
AU - Vennerstrom, Jonathan L.
PY - 2003/7/3
Y1 - 2003/7/3
N2 - Unlike diprotic chloroquine (CQ), its two 4-aminoquinoline carbon isosteres (1, 2) are monoprotic at physiological pH. Compared to CQ, hematin binding affinity of 1 decreased 6.4-fold, and there was no measurable binding for 2. Although 1 was a weak inhibitor of hemozoin formation, neither isostere inhibited P. falciparum in vitro. Evidently, the CQ-hematin interaction is largely a function of its pyridine substructure, but inhibition of hemozoin formation and parasite growth depends on its 4-aminopyridine substructure.
AB - Unlike diprotic chloroquine (CQ), its two 4-aminoquinoline carbon isosteres (1, 2) are monoprotic at physiological pH. Compared to CQ, hematin binding affinity of 1 decreased 6.4-fold, and there was no measurable binding for 2. Although 1 was a weak inhibitor of hemozoin formation, neither isostere inhibited P. falciparum in vitro. Evidently, the CQ-hematin interaction is largely a function of its pyridine substructure, but inhibition of hemozoin formation and parasite growth depends on its 4-aminopyridine substructure.
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U2 - 10.1021/jm030038x
DO - 10.1021/jm030038x
M3 - Article
C2 - 12825955
AN - SCOPUS:0038143278
SN - 0022-2623
VL - 46
SP - 3166
EP - 3169
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 14
ER -