Synthesis and Antimalarial Activities of Fluoroalkyl Derivatives of Dihydroartemisinin

Nga, Truong Thi Thanh; Ménage, Céline; Bégué, Jean‐Pierre; Bonnet‐Delpon, Danièle; Gantier, Jean-Charles; Pradines, Bruno; Doury, J. C.; Thac, Truong Dinh

doi:10.1021/jm9810147

Cited by 47 publications

(19 citation statements)

References 23 publications

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“…Artemisinin, a sesquiterpene lactone drug in the peroxide group, is extracted from the leaves of the Artemisia annua plant and used for the treatment of malaria. Its semisynthetic derivative dihydroartemisinin (DHA) is able to interact with Fe 2+ to generate reactive oxygen species (ROS) causing cytotoxicity [ 115 ], potentially reducing or eliminating the multidrug resistance of traditional chemotherapy agents. However, the lack of Fe 3+ and synchronous delivery of DHA and Fe 3+ in cancer cells make this therapeutic method a dilemma.…”

Section: Fe 3 O 4 Nps For Tamentioning

confidence: 99%

Fe3O4 Nanoparticles in Targeted Drug/Gene Delivery Systems

2018

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Fe3O4 nanoparticles (NPs), the most traditional magnetic nanoparticles, have received a great deal of attention in the biomedical field, especially for targeted drug/gene delivery systems, due to their outstanding magnetism, biocompatibility, lower toxicity, biodegradability, and other features. Naked Fe3O4 NPs are easy to aggregate and oxidize, and thus are often made with various coatings to realize superior properties for targeted drug/gene delivery. In this review, we first list the three commonly utilized synthesis methods of Fe3O4 NPs, and their advantages and disadvantages. In the second part, we describe coating materials that exhibit noticeable features that allow functionalization of Fe3O4 NPs and summarize their methods of drug targeting/gene delivery. Then our efforts will be devoted to the research status and progress of several different functionalized Fe3O4 NP delivery systems loaded with chemotherapeutic agents, and we present targeted gene transitive carriers in detail. In the following section, we illuminate the most effective treatment systems of the combined drug and gene therapy. Finally, we propose opportunities and challenges of the clinical transformation of Fe3O4 NPs targeting drug/gene delivery systems.

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Section: Fe 3 O 4 Nps For Tamentioning

confidence: 99%

Fe3O4 Nanoparticles in Targeted Drug/Gene Delivery Systems

2018

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“…On the other hand, the Mitsunobu reaction was advantageous for the acetalization of the antimalarial drug dihydroartemisinin 106 to give 107 with trifluoroethanol, having a p K a of 12.4 ( Scheme 19 ) [ 77 ]. The efficiency of the Mitsunobu glycosylation with fluorinated alcohols with p K a values between 9 and 12 was demonstrated with several other examples [ 78 ].…”

Section: Reviewmentioning

confidence: 99%

Anomeric modification of carbohydrates using the Mitsunobu reaction

Hain¹,

Rollin²,

Klaffke³

et al. 2018

Beilstein J. Org. Chem.

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The Mitsunobu reaction basically consists in the conversion of an alcohol into an ester under inversion of configuration, employing a carboxylic acid and a pair of two auxiliary reagents, mostly triphenylphosphine and a dialkyl azodicarboxylate. This reaction has been frequently used in carbohydrate chemistry for the modification of sugar hydroxy groups. Modification at the anomeric position, leading mainly to anomeric esters or glycosides, is of particular importance in the glycosciences. Therefore, this review focuses on the use of the Mitsunobu reaction for modifications of sugar hemiacetals. Strikingly, unprotected sugars can often be converted regioselectively at the anomeric center, whereas in other cases, the other hydroxy groups in reducing sugars have to be protected to achieve good results in the Mitsunobu procedure. We have reviewed on the one hand the literature on anomeric esterification, including glycosyl phosphates, and on the other hand glycoside synthesis, including S- and N-glycosides. The mechanistic details of the Mitsunobu reaction are discussed as well as this is important to explain and predict the stereoselectivity of anomeric modifications under Mitsunobu conditions. Though the Mitsunobu reaction is often not the first choice for the anomeric modification of carbohydrates, this review shows the high value of the reaction in many different circumstances.

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“…A recent approach to design more metabolically stable artemisinins has been developed by introducing a trifluoromethyl group at C-10 [71]. Due to its electron-withdrawing character, this substituent was expected to protect efficiently artemisinins from oxidative and hydrolytic cleavages, and from glucuronidation when a hydroxyl is present at C-10.…”

Section: Artemisininmentioning

confidence: 99%

“…This approach has led to preclinical development of the orally active 10-trifluoromethyl dihydroartemisinin (TDR 9706) and a 10-trifluoromethyl deoxoartemisinin (TDR 22706) (Fig. 38) [71,73].…”

Section: Artemisininmentioning

confidence: 99%