Facile synthesis and anticancer activity of C-10 non-acetal deoxoartemisinin dimers

Phothongkam, Supannee; Chancharunee, Sirirat; Saovapakhiran, Angkana; Wichai, Uthai; Pohmakotr, Manat

doi:10.1016/j.bmcl.2012.10.020

Cited by 4 publications

(5 citation statements)

References 26 publications

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“…As their IC 50 values ranged between 2.04 and 8.03 μM, the hybrids were at least 3-fold more active than dihydroartemisinin (IC 50 of 26.87 μM) (Table ). The results of this study indicated that the application of a (2-aminoethyl)glycine backbone connected to a C-10 nonacetal deoxoartemisinin yielded hybrids that were active against Caco-2 cells (IC 50 value of 2.87 μM for dimer 43b ). This effect can subsequently be improved upon by the introduction of other amino acids, such as lysine, to further increase the hybrid’s activity (IC 50 of 2.04 μM for hybrid 43d ).…”

Section: Anticancer Activitiesmentioning

confidence: 86%

“…Using direct reaction of two different artemisinin derivatives, the groups of Posner, Thebtaranonth, O’Neill, N’Da, Woerdenbag, Pras, Jung, Gong, Barua, Chancharunee, Sasaki were able to synthesize the following dimers (Figure ): dimer 32 containing an aromatic methoxy unit as linker, furan-linked dimer 33 , dimers linked on C-16 position 34a – g , amide-linked dimer 35 , amine-linked triazine dimers 36a – f , ether dimers 37a/b , amide dimers 38a/b and 39 containing a free amine unit, thioether dimer 40 , artemisinin-guanidine dimers 41a – h , dimers 42a/b containing a triazole unit as linker, N -protected amino acid ester dimers 43a – e , amine-linked dimers 44a – f . The antimalarial and anticancer activity of these dimers will be discussed in sections and .…”

Section: Different Synthetic Approaches To Artemisinin-derived Dimersmentioning

confidence: 99%

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Artemisinin-Derived Dimers: Potent Antimalarial and Anticancer Agents

et al. 2016

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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.

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Section: Anticancer Activitiesmentioning

confidence: 86%

Section: Different Synthetic Approaches To Artemisinin-derived Dimersmentioning

confidence: 99%

Artemisinin-Derived Dimers: Potent Antimalarial and Anticancer Agents

et al. 2016

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“…68 A solution phase peptide synthesis approach was applied to prepare dimers 51a-e (Table 4). 80 At first, 10-β-carboxylalkyldeoxoartemisinin was coupled to a N-(2-aminoethyl) glycine derived precursor in DMF using HATU as the coupling reagent. Afterward, the N-or C-terminus of precursor was deprotected, respectively using 20% piperidine/DMF or TFA/CH 2 Cl 2 and a coupling reaction between both molecules led to dimer 51b that was evaluated for its anticancer potential.…”

Section: Anticancer Activitymentioning

confidence: 99%

“…The study also provided possibilities for further improvement of cytotoxicity by introducing lysine on the backbone as seen in hybrid 51d (IC 50 = 2.04 µM). 80 The preliminary growth inhibitory activities of dimer 52 and 53b were tested at the NCI. Both were found to be selective and effective against leukemia (HL 60), non-small-cell lung cancer (NCI-H226), colon cancer (COLO-205 and KM-12) and CNS cancer (SF-295) cell lines.…”

Section: Anticancer Activitymentioning

confidence: 99%

Artemisinin‐derived dimers from a chemical perspective

Çapcı

Herrmann

Kumar

et al. 2021

Medicinal Research Reviews

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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.

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“…The majority of artemisinin dimers 13 and artemisinin were inactive against A375, A549, SH‐SY5Y, HCT116, and PC12 cancer cell lines, whereas compound 13a (IC 50 : 5.75–20.02 μM) not only possessed broad‐spectrum activity against all tested cancer cell lines but also demonstrated nontoxicity toward normal L02 cells . The dimers 14 (IC 50 : 2.04–8.03 μM, MTT assay) displayed considerable activity against Caco‐2 cancer cells, and all of them were more active than dihydroartemisinin (IC 50 : 26.87 μM) …”

Section: Amine‐/amide‐tethered Artemisinin‐derived Dimersmentioning

confidence: 99%

Artemisinin‐derived dimers as potential anticancer agents: Current developments, action mechanisms, and structure–activity relationships

Zhang

2019

Archiv der Pharmazie

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Anticancer agents play a pivotal role in cancer treatment. However, most of the anticancer drugs currently used in the clinics have a severe anticancer scenario, as well as low specificity and fatal side effects. Thus, there is an urgent demand to develop novel drugs with great efficacy, high specificity, and low side effects.Artemisinin and its semisynthetic derivatives are mainstays of chemotherapy against malaria, and artemisinin-based compounds, especially artemisinin-derived dimers, also exhibit excellent in vitro and in vivo anticancer activity. The structure-activity relationship (SAR) demonstrated that the linker between the two artemisinin moieties influenced the anticancer activity significantly; so, the rational design of the linker may provide valuable therapeutic intervention for the treatment of cancer.This review outlines the potential anticancer activity of artemisinin-derived dimers tethered by different linkers. The SARs, as well as mechanisms of action, are discussed to provide insights for the rational design of more effective dimers.

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Facile synthesis and anticancer activity of C-10 non-acetal deoxoartemisinin dimers

Cited by 4 publications

References 26 publications

Artemisinin-Derived Dimers: Potent Antimalarial and Anticancer Agents

Artemisinin-Derived Dimers: Potent Antimalarial and Anticancer Agents

Artemisinin‐derived dimers from a chemical perspective

Artemisinin‐derived dimers as potential anticancer agents: Current developments, action mechanisms, and structure–activity relationships

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