Synthesis And Anti-malarial Activity In Vivo Of Naphthoquine Derivatives

Naphthoquine (NQ) is a4’-hydroxyphenyl amino quinoline antimalarial developed in our lab. It is indicated that NQ has a high efficacy and good compliance of patients owe to its long half-life. Combined with artemisinin, it is a new fixed-dose ACT named ARCO(?) which is the only single-dose ACT available at present. Long half-life also make resistance formed easier. Experimental results show that the resistant mechanism of NQ is same with CQ. To afford multiple selections is necessary by searching for novel derivates base on NQ.We chose three kinds of terminal side chains to carry out modification terminal side chain with mannich base derivatives on phenol hydroxyl ortho-position of NQ:long chain alkoxy amines, long chain hydroxy-alkyl-amine, nitric heterocyclic ring compounds.We synthesized25new derivatives and determined their meting points (mp). The1H NMR and Mass Spectra were obtained to certify structure. All compounds were tested in vitro against parasite strains K173using’4-day inhibiton assays’and calculate the ED50.The ED50of Compound11is similar with NQ while compound20is less than NQ. The change on structure shows little relevant with anti-malarial activity.