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.

Characterization of Plasmodium Liver Stage Inhibition by Halofuginone

“…1) is important for antimalarial activity [16] but the substituent can be replaced with a pyrrolidine ring without a decrease in efficacy. [17] In this work, two N -acylated halofuginone derivatives (Fig. 1) were tested for the ability to reduce P. berghei sporozoite load in HepG2 cells.…”

ATP-directed capture of bioactive herbal-based medicine on human tRNA synthetase

“…MAZ1310) 8 . In contrast, derivatives that replaced the piperidine ring by the pyrrolidine ring of proline retained the similar or superior biological activity that was tested 14 .…”

Interactions of AChE with A? Aggregates in Alzheimer?s Brain: Therapeutic Relevance of IDN 5706

“…AChE activity is lower in most regions of AD brains, but it is increased within and around amyloid plaques (Geula and Mesulam, 1989b; Beach et al, 2000). The different molecular forms of AChE are altered in AD, showing a decrease in the tetrameric AChE G 4 isoform localized at central synapses (Xie et al, 2010), while the minor light forms (dimers G 2 and monomers G 1 ) increase (Atack et al, 1983; Saez-Valero et al, 1999). Interestingly, the activity of the light forms appears to increase in the most severely affected cases (Arendt et al, 1992).…”