Advocacy for the Medicinal Plant Artabotrys hexapetalus (Yingzhao) and Antimalarial Yingzhaosu Endoperoxides

Abstract

The medicinal plant Artabotrys hexapetalus (synonyms: A. uncinatus and A. odoratissimus) is known as yingzhao in Chinese. Extracts of the plant have long been used in Asian folk medicine to treat various symptoms and diseases, including fevers, microbial infections, ulcers, hepatic disorders and other health problems. In particular, extracts from the roots and fruits of the plant are used for treating malaria. Numerous bioactive natural products have been isolated from the plant, mainly aporphine (artabonatines, artacinatine) and benzylisoquinoline (hexapetalines) alkaloids, terpenoids (artaboterpenoids), flavonoids (artabotrysides), butanolides (uncinine, artapetalins) and a small series of endoperoxides known as yingzhaosu A-to-D. These natural products confer antioxidant, anti-inflammatory and antiproliferative properties to the plant extracts. The lead compound yingzhaosu A displays marked activities against the malaria parasites Plasmodium falciparum and P. berghei. Total syntheses have been developed to access yingzhaosu compounds and analogues, such as the potent compound C14-epi-yingzhaosu A and simpler molecules with a dioxane unit. The mechanism of action of yingzhaosu A points to an iron(II)-induced degradation leading to the formation of two alkylating species, an unsaturated ketone and a cyclohexyl radical, which can then react with vital parasitic proteins. A bioreductive activation of yingzhaosu A endoperoxide can also occur with the heme iron complex. The mechanism of action of yingzhaosu endoperoxides is discussed, to promote further chemical and pharmacological studies of these neglected, but highly interesting bioactive compounds. Yingzhaosu A/C represent useful templates for designing novel antimalarial drugs.

Research Progress on Sesquiterpene Compounds from Artabotrys Plants of Annonaceae

“…Firstly, in the presence of oxygen and iron (II), yingzhaosu A will undergo a degradation reaction due to the induction of iron (II), forming unsaturated ketones and cyclohexyl radicals, respectively. The active substances produced in this process may be the reason for its antimalarial effect [120].…”

Engineering Amino Acid and Peptide Supramolecular Architectures through Fluorination

“…In contrast, incorporation of aromatic fluorinated residues mostly results in retained or decreased proteolytic stability [12] . Additionally, molecular pre‐organization induced by fluorination can favor specific noncovalent interactions between F−AAs or F−peptides and their biological targets, resulting in higher binding affinity and selectivity [5,13] . Some F−AAs were reported to improve the antimicrobial efficacy of peptide‐based antibacterial agents.…”

“…The perturbation of molecular structures and intermolecular interactions exerted by fluorine atoms starts affecting the self‐assembly behavior of single amino acids, then passes through the secondary structure of peptides, and finally reaches tertiary and quaternary structures of proteins [4] . It is, thus, not surprising that, among all biologically relevant compounds, several research efforts have been devoted to the synthesis of fluorinated amino acids (F−AAs), that often show improved stability, enhanced aggregation tendency, and tunable properties, compared to naturally occurring ones [5] . Many synthetic strategies were optimized to incorporate fluorine into aa, mainly through chemical modification of their sidechains [6,7] .…”

Complete chloroplast genome of Artabotrys hexapetalus (L.f.) Bhandari 1965 (Annonaceae)

“…Despite substantial research into the chemical composition of Artabotrys hexapetalus (Xi et al. 2016 , 2017 ; Bailly and Hénichart 2022 ), the studies of its chloroplast (cp) genome still need to be expanded. It is understood that chloroplast, essential organelles in plants housing a distinct genome, have been extensively employed in plant phylogenetic analysis (Cheng et al.…”