Synthesis and in vitro evaluation of hydrazinyl phthalazines against malaria parasite, Plasmodium falciparum. Issue 14 (15th July 2016)

• Record Type: Journal Article
• Authors: Subramanian, Gowtham; Babu Rajeev, C.P.; Mohan, Chakrabhavi Dhananjaya; Sinha, Ameya; Chu, Trang T.T.; Anusha, Sebastian; Ximei, Huang; Fuchs, Julian E.; Bender, Andreas; Rangappa, Kanchugarakoppal S.; Chandramohanadas, Rajesh; Basappa,
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 14(2016)
• Page Start: 3300
• Page End: 3306
• Publication Date: 2016-07-15
• Subjects: Hydralazines -- Antimalarials -- Dihydroorotate dehydrogenase -- P. falciparum -- Bronsted acidic ionic liquids; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.05.049
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: In this report, we describe the synthesis of 1-(Phthalazin-4-yl)-hydrazine using bronsted acidic ionic liquids and demonstrate their ability to inhibit asexual stage development of human malaria parasite, Plasmodium falciparum . Through computational studies, we short-listed chemical scaffolds with potential binding affinity to an essential parasite protein, dihydroorotate dehydrogenase (DHODH). Further, these compounds were synthesized in the lab and tested against P. falciparum . Several compounds from our library showed inhibitory activity at low micro-molar concentrations with minimal cytotoxic effects. These results indicate the potential of hydralazine derivatives as reference scaffolds to develop novel antimalarials.