Synthesis of hybrid 4-anilinoquinoline triazines as potent antimalarial agents, their in silico modeling and bioevaluation as Plasmodium falciparum transketolase and -hematin inhibitorsElectronic supplementary information (ESI) available: Experimental procedures, characterization data, protocols of biological assays. See DOI: 10.1039/c1md00188d

• Main Authors: Sharma, Moni, Chauhan, Kuldeep, Chauhan, Shikha S, Kumar, Ashok, Singh, Shiv Vardan, Saxena, Jitendra K, Agarwal, Pooja, Srivastava, Kumkum, Raja Kumar, S, Puri, Sunil K, Shah, Priyanka, Siddiqi, M. I, Chauhan, Prem M. S
• Format: Article
• Language: English
• ISSN: 2040-2503; 2040-2511
• DOI: 10.1039/c1md00188d

Analogues of a novel class of hybrid 4-anilinoquinoline triazines have been synthesized with the aim of identifying the compounds with improved antimalarial activity preserving the potency of parent drug chloroquine (CQ). All the synthesized molecules were evaluated in vitro for their antimalarial activity against chloroquine-sensitive 3D7 and chloroquine-resistant K1 strains of P. falciparum. Molecules were also screened for their cytotoxicity towards VERO cell line. Sixteen compounds ( 17 , 19 , 26 , 27 , 29 , 31 , 32 , 33 , 35 , 36 , 37 , 39 , 40 , 49 , 50 , and 52 ) exhibited excellent antimalarial activity with IC 50 values ranging from 1.364.63 ng ml 1 and were also found to be nontoxic with good selectivity index. In silico activity prediction as well as enzyme inhibitory activity against P. falciparum transketolase reveals that the molecules are also good inhibitors of the enzyme P. falciparum transketolase. The compound 52 showed good in vivo activity by oral route and resulted in survival of 3 out of 5 mice till day 28. Synthesis and bioevaluation of novel anilinoquinoline-triazine hybrids as potent antimalarial agents are reported.