N-Piperonyl substitution on aminoquinoline-pyrimidine hybrids: Effect on the antiplasmodial potency.
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 IC50values 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.
Department of Chemistry, University of Delhi, Delhi 110007, India.
Rohit
R
Kholiya
National Centre for Natural Products Research, University of Mississippi, MS 38677, USA.
Shabana I
SI
Khan
Department of Chemistry, University of Delhi, Delhi 110007, India.
Aparna
A
Bahuguna
Department of Chemistry, University of Delhi, Delhi 110007, India.
Mohit
M
Tripathi
Department of Chemistry, University of Delhi, Delhi 110007, India. Electronic address: dsrawat@chemistry.du.ac.in.
Diwan S
DS
Rawat
D000634:Aminoquinolines / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D008958:Models, Molecular; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014709:Vero Cells
D000634:Aminoquinolines; D000962:Antimalarials; D011743:Pyrimidines; C030986:pyrimidine
Aminoquinoline; Antimalarial; Hybrids; Piperonyl; Plasmodium falciparum; Pyrimidine