Kashyap, et al.: Antimalarial Activity of Quinoline-Lawsone HybridsIn the present study, a new series of quinoline-lawsone hybrid compounds were synthesized and evaluated in vitro for their antimalarial effectiveness. Several aliphatic and aromatic/heteroaromatic diamines were used as connecting/bridge moiety between the 7-chloro-4-aminoquinoline and 3-amino-1, 4-naphthoquinone pharmacophoric scaffolds. The molecular properties of hybrid compounds were also studied in silico for drug-likeness assessment based on Lipinski's rule of five. Results of antimalarial activity reveal that all the tested compounds showed activity against both chloroquine sensitive (RKL-2) and chloroquine resistant (RKL-9) strains of Plasmodium falciparum which was considerably less as compared to the standard drug, chloroquine. All the compounds exhibited same degree of activity at the tested dose against sensitive strain with IC 50 values 0.391-1.033 µg/ml. Furthermore, four compounds which were additionally tested against resistant strain also showed activity with IC 50 values from 0.684 to 1.778 µg/ml at the same dose. The IC 50 values for CQ against sensitive and resistant strains of P. falciparum were found to be 0.0391 µg/ml and 0.305 µg/ml, respectively. From results it is apparent that the compound with a small alkyl bridge moiety diaminoethyl possesses better activity profile against both sensitive and resistant strains (IC 50 =0.391 and 0.684 µg/ml, respectively) than rest of the synthesized analogues. The results of drug-likeness studies showed that all newly designed quinoline-lawsone hybrids possess good drug-like properties, indicating their druglikeness behaviour is favourable for optimal antimalarial action. Assessment of drug-likeness score further implies the suitability of hybrid derivatives as drug-like molecules.Key words: Quinoline, lawsone, hybrid, bridge moiety, Plasmodium falciparum, resistant malariaOver the last few decades, the burden of malaria has increasingly become a serious health concern around the globe. The disease remains one of the most lethal infectious diseases of human beings affecting around 300-600 million people with about three million deaths per year globally [1] . Plasmodium falciparum is the most prevalent and deadly species among all malaria parasites, which causes severe complicated malaria such as cerebral malaria, and is responsible for most of the malaria-related deaths worldwide. Recent emergence of multidrug-resistant strains of P. falciparum has further complicated the issues of treating malaria using currently available antimalarial drugs [2][3][4] . However, with the development of novel and potent antimalarial agents the above challenging issue could be addressed.Chloroquine (CQ, fig. 1), a 4-aminoquinoline synthetic antimalarial, was once a highly potent drug against malaria. Literature reports suggest that 7-chloro-4-aminoquinoline nucleus of 4-aminoquinoline antimalarial drugs is responsible for their antimalarial action which could be attributed mainly due to the prevention o...