title: Synthesis and biological evaluation of febrifugine analogues as potential antimalarial agents.
abstract: Febrifugine is an alkaloid isolated from Dichroa febrifuga Lour as the active component against Plasmodium falciparum. Adverse side effects have precluded febrifugine as a potential clinical drug. In this study novel febrifugine analogues were designed and synthesized. Lower toxicity was achieved by reducing or eliminating the tendency of forming chemically reactive and toxic intermediates and metabolites. Synthesized compounds were evaluated for acute toxicity and in vitro and in vivo antimalarial efficacy. Some compounds are much less toxic than the natural product febrifugine and existing antimalarial drug chloroquine and are expected to possess wide therapeutic windows. These compounds, as well as the underlying design rationale, may find usefulness in the discovery and development of new antimalarial drugs.
authors.affiliation: Radix Pharmaceuticals, Inc, Potomac, MD 20854, USA. shuren.zhu@gmail.com
authors.forename: Shuren
authors.initials: S
authors.lastname: Zhu
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.forename: Chandrashekar
authors.initials: C
authors.lastname: Gudise
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.forename: Erika
authors.initials: E
authors.lastname: Smith
authors.forename: Yuling
authors.initials: Y
authors.lastname: Zeng
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use* / Q000633:toxicity; D004353:Drug Evaluation, Preclinical; D029628:Hydrangeaceae / Q000737:chemistry; D008288:Malaria / Q000188:drug therapy*; D051379:Mice; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use* / Q000633:toxicity; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000502:physiology; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use* / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D010880:Piperidines; D011799:Quinazolines; C001207:febrifugine