N-Piperonyl substitution on aminoquinoline-pyrimidine hybrids: Effect on the antiplasmodial potency.

Authors :: Kholiya R
Khan SI
Bahuguna A
Tripathi M
Rawat DS
Source :: European journal of medicinal chemistry [Eur J Med Chem] 2017 May 05; Vol. 131, pp. 126-140. Date of Electronic Publication: 2017 Mar 11.
Publication Year :: 2017
Abstract: A series of 4-aminoquinoline-piperonyl-pyrimidine hybrids were synthesized with the aim of identifying compounds with enhanced antimalarial activity. All the synthesized molecules were evaluated in vitro against cultured Plasmodium falciparum W2 and D6 strains and exhibited potent antiplasmodial activities with IC <subscript>50</subscript> values in the range of 0.02-5.16 μM. Out of the 22 synthesised hybrids, 12 were found to be better (up to eight-fold more active) than chloroquine (CQ), particularly against the CQ-resistant W2 strain of P. falciparum with no significant cytotoxicity towards the mammalian cells. Mechanistic studies reveal that these compounds bind with heme and computational docking studies showed good docking interactions within the active site of Pf-DHFR.<br /> (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Subjects :: Aminoquinolines chemistry
Animals
Antimalarials chemical synthesis
Antimalarials chemistry
Chlorocebus aethiops
Dose-Response Relationship, Drug
Models, Molecular
Molecular Structure
Parasitic Sensitivity Tests
Pyrimidines chemistry
Structure-Activity Relationship
Vero Cells
Aminoquinolines pharmacology
Antimalarials pharmacology
Plasmodium falciparum drug effects
Pyrimidines pharmacology

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