4-Aminoquinoline derivatives: Synthesis, in vitro and in vivo antiplasmodial activity against chloroquine-resistant parasites

TY - JOUR

T1 - 4-Aminoquinoline derivatives

T2 - Synthesis, in vitro and in vivo antiplasmodial activity against chloroquine-resistant parasites

AU - Singh, Shailja

AU - Agarwal, Drishti

AU - Sharma, Kumkum

AU - Sharma, Manish

AU - Nielsen, Morten A

AU - Alifrangis, Michael

AU - Singh, Ashok K

AU - Gupta, Rinkoo D

AU - Awasthi, Satish K

N1 - Copyright © 2016 Elsevier Masson SAS. All rights reserved.

PY - 2016/10/21

Y1 - 2016/10/21

N2 - Synthetic quinoline derivatives continue to be considered as candidates for new drug discovery if they act against CQ-resistant strains of malaria even after the widespread emergence of resistance to CQ. In this study, we explored the activities of two series of new 4-aminoquinoline derivatives and found them to be effective against Plasmodium falciparum under in vitro conditions. Further, we selected four most active derivatives 1m, 1o, 2c and 2j and evaluated their antimalarial potential against Plasmodium berghei in vivo. These 4-aminoquinolines cured BALB/c mice infected with P. berghei. The ED50 values were calculated to be 2.062, 2.231, 1.431, 1.623 and 1.18 mg/kg of body weight for each of the compounds 1m, 1o, 2c, 2j and amodiaquine, respectively. Total doses of 500 mg/kg of body weight were well received. The study suggests that these new 4-aminoquinolines should be used for structure activity relationship to find lead molecules for treating multidrug-resistant Plasmodium falciparum and Plasmodium vivax.

AB - Synthetic quinoline derivatives continue to be considered as candidates for new drug discovery if they act against CQ-resistant strains of malaria even after the widespread emergence of resistance to CQ. In this study, we explored the activities of two series of new 4-aminoquinoline derivatives and found them to be effective against Plasmodium falciparum under in vitro conditions. Further, we selected four most active derivatives 1m, 1o, 2c and 2j and evaluated their antimalarial potential against Plasmodium berghei in vivo. These 4-aminoquinolines cured BALB/c mice infected with P. berghei. The ED50 values were calculated to be 2.062, 2.231, 1.431, 1.623 and 1.18 mg/kg of body weight for each of the compounds 1m, 1o, 2c, 2j and amodiaquine, respectively. Total doses of 500 mg/kg of body weight were well received. The study suggests that these new 4-aminoquinolines should be used for structure activity relationship to find lead molecules for treating multidrug-resistant Plasmodium falciparum and Plasmodium vivax.

KW - Faculty of Health and Medical Sciences

KW - Antimalarial

KW - Amodiaquine

KW - Chloroquine

KW - 4-Aminoquinoline analogues

KW - Plasmodium falciparum

KW - Plasmodium berghei

U2 - 10.1016/j.ejmech.2016.06.033

DO - 10.1016/j.ejmech.2016.06.033

M3 - Journal article

C2 - 27394399

SN - 0223-5234

VL - 122

SP - 394

EP - 407

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

ER -