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

Research output: Contribution to journalJournal articleResearchpeer-review

Shailja Singh, Drishti Agarwal, Kumkum Sharma, Manish Sharma, Morten A Nielsen, Michael Alifrangis, Ashok K Singh, Rinkoo D Gupta, Satish K Awasthi

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.
Original languageEnglish
JournalEuropean Journal of Medicinal Chemistry
Volume122
Pages (from-to)394-407
Number of pages14
ISSN0223-5234
DOIs
Publication statusPublished - 21 Oct 2016

ID: 163764105