Artemisinin‐derived dimers from a chemical perspective

Abstract

Considerable progress has been made with the rather recently developed dimer approach, which has already found applications in the development of new effective artemisinin-derived antimalarial, anticancer, and antiviral agents. One observation common to these potential applications is the significant (i.e., much more than double) improvement in activity of artemisinin based dimers, which are not toxic to normal cells and have fewer or less harmful side effects, with respect to monomers against parasites, cancer cells and viruses. Due to the high potential of the dimerization concept, many new artemisinin-derived dimer compounds and their biological activities have been recently reported. In this review an overview of the synthesis of dimer drug candidates based on the clinically used drug artemisinin and its semisynthetic derivatives is given.Besides the highlighting of biological activities of the selected dimers, the main focus is set on different synthetic approaches toward the dimers containing a broad variety of symmetric and nonsymmetric linking moieties.

Design and synthesis of eugenol/isoeugenol glycoconjugates and other analogues as antifungal agents against Aspergillus fumigatus

“…It is well established that often dimers of biologically active molecules exhibit higher activity than the monomeric unit. 28,29 With compound 14 at hand, we envisaged to synthesize dimeric compounds. In this regard, we treated compound 14 with compounds 8, 3, and 4 via a click reaction to afford compounds 15, 16, and 17, respectively (Scheme 5).…”

The current scenario on anticancer activity of artemisinin metal complexes, hybrids, and dimers

“…[70,71] Many ART dimers exhibited higher anticancer potential than the corresponding mono-counterparts, demonstrating the potential of ART dimers as putative anticancer agents. [72,73] The curcumin tethered artesunate dimer 42 (Figure 7; IC 50 : 1.37-3.43 µM, MTT assay) exhibited potent activity against HeLa, SK-MEL3, SK-MEL24, and RPMI-7951 cancer cell lines and was nontoxic (IC 50 : >300 µM) towards normal human primary fibroblast cell line (C3PV). [74] The SAR illustrated that curcumin linker was not crucial for the activity, and replacement by tyrosol could enhance the activity against SK-MEL24 and RPMI-7951 cells (43, IC 50 : 0.24 and 0.49 µM) [74] ; conversion of phenol to benzyl alcohol was permitted, and dimer 44 (IC 50 : 0.05-2.40 µM, MTT assay) also demonstrated promising activity against MDA-MB-231, RPMI7951 and RPMI7951-DFO cancer cell lines [75] ; the ester linker can be replaced by amide, and hybrid dimer 45 (IC 50 :…”

“…[ 70,71 ] Many ART dimers exhibited higher anticancer potential than the corresponding mono‐counterparts, demonstrating the potential of ART dimers as putative anticancer agents. [ 72,73 ]…”

The antimalarial activity of 1,2,4‐trioxolane/trioxane hybrids and dimers: A review

“…Dimerization is a promising strategy to extend the biological spectrum, increase the activity, conquer drug resistance, and improve pharmacological as well as pharmacokinetic profiles. [63,64] Accordingly, dimerization of ART may provide valuable therapeutic intervention for the treatment of malaria.…”