Docking, synthesis and antimalarial activity of novel 4-anilinoquinoline derivatives. Issue 8 (15th April 2017)

• Record Type: Journal Article
• Authors: Vijayaraghavan, Shilpa; Mahajan, Supriya
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 8(2017)
• Page Start: 1693
• Page End: 1697
• Publication Date: 2017-04-15
• Subjects: Malaria -- Plasmodium falciparum -- Falcipain-2 -- Cysteine protease -- 4-Anilinoquinoline triazine -- β-Haematin; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.03.005
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: Falcipain-2 and β-haematin are the promising targets for antimalarial activity. All compounds showed better G-score and in vivo activity compared to chloroquine. Twelve compounds exhibited in vitro inhibition better than that of chloroquine. Ten compounds exhibited β-haematin inhibition better than that of chloroquine. Compound3k showed excellent in vitro and β-haematin inhibitory activity. Abstract: 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 IC50 values in the range of 18–25 µM. 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.