Artemisinin-Derived Dimers: Potent Antimalarial and Anticancer Agents

Abstract

The development of new efficient therapeutics for the treatment of malaria and cancer is an important endeavor. Over the past 15 years, much attention has been paid to the synthesis of dimeric structures, which combine two units of artemisinin, as lead compounds of interest. A wide variety of atemisinin-derived dimers containing different linkers demonstrate improved properties compared to their parent compounds (e.g., circumventing multidrug resistance), making the dimerization concept highly compelling for development of efficient antimalarial and anticancer drugs. The present Perspective highlights recent developments on different types of artemisinin-derived dimers and their structural and functional features. Particular emphasis is put on the respective in vitro and in vivo studies, exploring the role of the length and nature of linkers on the activities of the dimers, and considering the future prospects of the dimerization concept for drug discovery.

Artemisinin as an anticancer drug: Recent advances in target profiling and mechanisms of action

“…In the same vein, novel formulations such as synthetic dimers, trimers, and drug hybrids with quinolines as well as other compounds have also emerged as viable methods of drastically enhancing drug effectiveness as well as overcoming drug resistance and improving pharmacokinetic properties. Many of these synthetic derivatives have been extensively reviewed by the Tsogoeva group …”

Facile access to potent antiviral quinazoline heterocycles with fluorescence properties via merging metal-free domino reactions

“…Prevention and clinical interventions for HCMV disease are limited, since cross-resistance to all approved anti-HCMV drugs is increasingly observed31. As alternatives to standard drugs2332, our ongoing search for highly active hybrid molecules333435, which exceed their parent compounds in activity against HCMV, resulted in synthesis of new artesunic acid–quinazoline hybrids 8 and 9 (Fig. 7a and Supplementary Methods).…”

“…6) as coupling partners, since their fluorescence properties were considered beneficial for biological investigations. Artesunic acid on the other hand was selected because it proved to be a valuable building block in order to get highly bioactive compounds with just a few chemical transformations and also because of its promising pharmacological properties233235.…”

Spiroverknüpfte und ringanellierte 1,2,4‐Trioxepan‐, 1,2,4‐Trioxocan‐ und 1,2,4‐Trioxonan‐Cyclohexadienone: cyclische Peroxide mit ungewöhnlicher Ringkonformationsdynamik

“…[10] In jüngster Zeit wurden auch Flussmikroreaktionen eingesetzt, um grçßere Mengen an Artemisinin mittels Photooxygenierung herzustellen. [12] Außerdem wurden Dyaden (zusätzlich zu Hybriden oder dimeren Strukturen) [13] aus natürlichen Artemisininderivaten und synthetischen Trioxanen hergestellt. B.…”

“…13 C-NMR-Spektrum (Einschub: 1 H-NMR-Spektrum) des 1,2,4-Trioxonans 12 a in CD 3 OD (positive Signale CH und CH 3 ).…”