Molecular Hybridization as a Strategy for Developing Artemisinin-Derived Anticancer Candidates

Abstract

Artemisinin is a natural compound extracted from Artemisia species belonging to the Asteraceae family. Currently, artemisinin and its derivatives are considered among the most significant small-molecule antimalarial drugs. Artemisinin and its derivatives have also been shown to possess selective anticancer properties, however, there are several limitations and gaps in knowledge that retard their repurposing as effective anticancer agents. Hybridization resulting from a covalent combination of artemisinin with one or more active pharmacophores has emerged as a promising approach to overcome several issues. The variety of hybridization partners allows improvement in artemisinin activity by tuning the ability of conjugated artemisinin to interact with various molecule targets involved in multiple biological pathways. This review highlights the current scenario of artemisinin-derived hybrids with potential anticancer activity. The synthetic approaches to achieve the corresponding hybrids and the structure–activity relationships are discussed to facilitate further rational design of more effective candidates.

Dihydroartemisinin-Ursodeoxycholic Bile Acid Hybrids in the Fight against SARS-CoV-2

“…The greater antiviral activity displayed by hybrid DHA-t-UDCMe with respect to fused hybrid DHA-UDC may be attributable, in part, to the presence of the triazole ring. Indeed, the linker can also play a role in the biological activity of the hybrids . In particular, the triazole moiety is known to improve pharmacological, pharmacokinetic, and physiochemical profiles of active compounds, being somehow considered a pharmacophore itself.…”

“…Indeed, the linker can also play a role in the biological activity of the hybrids. 21 In particular, the triazole moiety is known to improve pharmacological, pharmacokinetic, and physiochemical profiles of active compounds, 47 being somehow considered a pharmacophore itself.…”

“…The development of artemisinin-derived hybrid molecules has been recognized as a valuable approach to overcoming these limitations. Indeed, many studies have been reported on artemisinin-derived hybrids as anticancer and antimalarial , candidates over the past decade. Molecular hybridization, based on the conjugation of bioactive molecules through covalent bonds, has been recognized to be an efficient tool to improve the stability, activity, selectivity, and safety profile as well as to overcome drug resistance with respect to the components .…”