Evidence for a Common Non‐Heme Chelatable‐Iron‐Dependent Activation Mechanism for Semisynthetic and Synthetic Endoperoxide Antimalarial Drugs

Antimalarial Mannoxanes: Hybrid Antimalarial Drugs with Outstanding Oral Activity Profiles and A Potential Dual Mechanism of Action

“…Thus, these molecules may have the capacity to target the parasite by two mechanisms; a chloroquine/amodiaquine-like heme binding action and an artemisinin-like action through reductive OÀO bond activation. [17] It should be added that Haynes and coworkers have recently proposed a "non-iron" activation mechanism whereby tetraoxanes have been shown to be efficient flavin oxidisers and this opens up an additional third potential mechanism of action for these interesting hybrids.…”

Rational design of Tamiflu derivatives targeting at the open conformation of neuraminidase subtype 1

“…Synthesis of some analogues has also been reported [60][61][62]. The feasible synthetic method for linking the Tamiflu scaffold and the furan moiety is given in Scheme 5 [63]. Considering the acid intermediate in the condensation reaction, compound 3 should be reduced to aldehyde first by diisobutylaluminium hydride (DIBAL-H), and then protected with glycol.…”

Highly potent artemisinin-derived dimers and trimers: Synthesis and evaluation of their antimalarial, antileukemia and antiviral activities

“…Hybrids 4, 5 and 6 were obtained by a Steglich esterification (DCM, DMAP and DCC at rt) of different artemisinin-derived precursors in yields ranging from 57% to quantitative (Scheme 1). The precursors DHA (2) and artesunic acid 3 are commercially available, artemisinin-derived acid 10, [40] di-artemisinin-derived alcohol 11 [41,42] and artemisinin-derived alcohol 12 [43] were prepared by literature known procedures. A published reaction protocol (TMSOTf, CHCl 3 , 0 °C) [44] yielded ether-hybrid 7 in 52% yield from dihydroartemisinin acetate 13 and alcohol 11.…”