Docking, synthesis and antimalarial activity of novel 4-anilinoquinoline derivatives.
A series of 4-anilinoquinoline triazine derivatives were designed, synthesized and screened for in vivo antimalarial activity against a chloroquine-sensitive strain of Plasmodium berghei. The compounds were further subjected to in vitro antimalarial activity against chloroquine-resistant W2 strain of Plasmodium falciparum and β-haematin inhibition studies. All the compounds exhibited in vivo antimalarial activity better than that shown by the standard drug, chloroquine. Twelve out of fifteen compounds showed better inhibition than that of chloroquine against chloroquine-resistant W2 strain of Plasmodium falciparum. Ten compounds showed β-haematin inhibition, better than that of chloroquine, with IC50values in the range of 18-25µM. One compound, 3k, was found to be better than artemisinin against W2 strain of Plasmodium falciparum and also displayed the best β-haematin inhibitory activity, thereby becoming eligible to be explored as a potential lead for antimalarial chemotherapy.
Department of Pharmaceutical Chemistry, C.U. Shah College of Pharmacy, S.N.D.T. Women's University, Sir Vithaldas Vidyavihar, Santacruz (W), Mumbai 400049, India. Electronic address: shilpa_vijayaraghavan@yahoo.co.in.
Shilpa
S
Vijayaraghavan
Department of Pharmaceutical Chemistry, C.U. Shah College of Pharmacy, S.N.D.T. Women's University, Sir Vithaldas Vidyavihar, Santacruz (W), Mumbai 400049, India.
Supriya
S
Mahajan
D000814:Aniline Compounds / Q000737:chemistry / Q000494:pharmacology; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D006420:Hemeproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D062105:Molecular Docking Simulation; D021261:Parasitic Sensitivity Tests; D010962:Plasmodium berghei / Q000187:drug effects* / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000378:metabolism; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000814:Aniline Compounds; D000962:Antimalarials; D006420:Hemeproteins; D015800:Protozoan Proteins; D011804:Quinolines; C020753:hemozoin; D003546:Cysteine Endopeptidases; C416224:falcipain 2
4-Anilinoquinoline triazine; Cysteine protease; Falcipain-2; Malaria; Plasmodium falciparum; β-Haematin