Design, synthesis and anti-breast cancer properties of butyric ester tethered dihydroartemisinin-isatin hybrids

Zhao, Shijia; Zhang, Xiaoyan; Tang, Min; Liu, Xiaocheng; Deng, Jiyong; Zhou, Wei; Xu, Zhi

doi:10.1007/s00044-023-03030-0

Cited by 5 publications

(11 citation statements)

References 23 publications

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“…We investigated the anti‐tumor activity of these compounds in MCF‐7 and HepG2 tumor cells to study their structure–activity relationship. Compared with DHA, which had an IC 50 of >10 μM in MCF‐7 and HepG2 tumor cells, [26, 27] the anti‐tumor derivatives with β , β and α , β configurations showed a remarkable improvement in anti‐tumor effect. Our results indicated that the β , β and α , β configurations were more effective in inhibiting tumor growth than the α , α configuration.…”

Section: Discussionmentioning

confidence: 99%

Design, Synthesis, and Antitumor Activities of Isomers of Artemisinin Dimer Derivatives

Yue

Pan

Wang

et al. 2023

Chemistry & Biodiversity

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In recent years, numerous studies have reported on the antitumor properties of artemisinin and its derivatives. However, the relationship between their artemisinin chirality and activity remains unknown. In this study, we synthesized a series of artemisinin dimer derivatives with three different chiral structures and tested their antiproliferative activity in MCF-7 and HepG2 cells using the CCK-8 assay. Interestingly, we discovered that artemisinin dimer derivatives with β, β and α, β conformations at C-10 exhibited stronger anti-tumor activity than those with an α, α configuration in MCF-7 and HepG2 cells. Notably, compound 4 showed an activity of 0.06 μM in MCF-7 cells. This study demonstrates the relationship between the conformation and activity of artemisinin dimer derivatives, and these derivatives have the potential to be developed into anti-cancer drugs.

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Section: Discussionmentioning

confidence: 99%

Design, Synthesis, and Antitumor Activities of Isomers of Artemisinin Dimer Derivatives

Yue

Pan

Wang

et al. 2023

Chemistry & Biodiversity

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“…[53] In addition, hybrid 21 (IC 50 : 48. 35 22.0-63.7 µM), revealing that the indole moiety was more favorable than the isatin motif. [54] The activity was negatively affected in hybrid 22 by the inclusion of a methoxy group into the para-position of phenyl ring.…”

Section: Indole/isatin-azole Hybridsmentioning

confidence: 99%

“…Additional research revealed that the linker between the isatin and dihydroartemisinin moieties was essential for the activity, and the incorporation of 1,2,3-triazole between the two pharmacophores reduced the activity based on the fact that hybrids 7 (IC 50 : 59.8->100 µM) exhibited marginal efficacy against MCF-7/ADR, MDA-MB-231, and MCF-7 BC cell lines, [31] whereas replacement of the ether linker by ester linker was permitted. [32][33][34][35] For the estertethered isatin-dihydroartemisinin hybrids 8, the SARs revealed that (1) the activity was remarkably impacted by the carbon spacer between the isatin and dihydroartemisinin moieties, and a shorter linker was usually more favorable than the longer ones; (2) the activity was boosted up by benzoxime at position C-3 of isatin motif; and (3) electron-donating group at C-5 position of isatin skeleton attenuated the activity. [32][33][34][35] Among them, hybrids 8a,b (IC 50 : 3.85-9.36 and 3.21-9.53 µM, respectively) were approximately ≥8.4 times more potent than dihydroartemisinin (IC 50 : 79.10 and 82.78 µM), artemisinin (IC 50 : >100 µM), and doxorubicin (IC 50 : >100 µM) against multidrugresistant MDA-MB-231/ADR and MCF-7/ADR cell lines.…”

Section: Isatin-dihydroartemisinin Hybridsmentioning

confidence: 99%

“…[32][33][34][35] For the estertethered isatin-dihydroartemisinin hybrids 8, the SARs revealed that (1) the activity was remarkably impacted by the carbon spacer between the isatin and dihydroartemisinin moieties, and a shorter linker was usually more favorable than the longer ones; (2) the activity was boosted up by benzoxime at position C-3 of isatin motif; and (3) electron-donating group at C-5 position of isatin skeleton attenuated the activity. [32][33][34][35] Among them, hybrids 8a,b (IC 50 : 3.85-9.36 and 3.21-9.53 µM, respectively) were approximately ≥8.4 times more potent than dihydroartemisinin (IC 50 : 79.10 and 82.78 µM), artemisinin (IC 50 : >100 µM), and doxorubicin (IC 50 : >100 µM) against multidrugresistant MDA-MB-231/ADR and MCF-7/ADR cell lines. [32] In addition, hybrids 8a,b (IC 50 : >100 µM) were found to have no toxicity against healthy MCF-10A breast cells.…”

Section: Isatin-dihydroartemisinin Hybridsmentioning

confidence: 99%

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The anti‐breast cancer potential of indole/isatin hybrids

Wang,

Huang,

Yuan

et al. 2023

Archiv der Pharmazie

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Breast cancer (BC) is one of the most prevalent malignancies and the major contributor to cancer mortality in women globally, with a high degree of heterogeneity and a dismal prognosis. As drug resistance is responsible for most BC fatalities and advanced BC is currently considered incurable, finding innovative anti‐BC chemotherapeutics is urgently required. Indole and its analog isatin (indole‐1H‐2,3‐dione) are prominent pharmacophores in the development of novel medications, and their derivatives exhibit strong anticancer activities, also against BC. In particular, indole/isatin hybrids exhibit significant potency against BC including multidrug‐resistant forms and excellent selectivity by influencing a variety of biological targets associated with the disease, supplying helpful building blocks for the identification of potential new BC treatment options. This review includes articles from 2020 to the present and provides insights into the in vitro and in vivo anti‐BC potential, molecular mechanisms, and structure–activity relationships (SARs) of indole/isatin hybrids that may be helpful in the development of innovative anti‐BC chemotherapeutics.

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“…Xu et al reported [ 88 , 89 ] a series of dihydroartemisinin–isatin hybrids conjugated through ester linkers of different lengths. In particular, dihydroartemisinin ( 2 ) was reacted with isatin carboxylic acid homologue derivatives 151a – d ( Scheme 28 ) and their C-5 derivatives substituted with fluorine, methyl and methoxy moieties.…”

Section: Artemisinin Hybrids Based On Natural and Synthetic Pharmacop...mentioning

confidence: 99%

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

Marchesi,

Perrone,

Navacchia

2023

Pharmaceutics

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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.

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Design, synthesis and anti-breast cancer properties of butyric ester tethered dihydroartemisinin-isatin hybrids

Cited by 5 publications

References 23 publications

Design, Synthesis, and Antitumor Activities of Isomers of Artemisinin Dimer Derivatives

Design, Synthesis, and Antitumor Activities of Isomers of Artemisinin Dimer Derivatives

The anti‐breast cancer potential of indole/isatin hybrids

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

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