A gram-scale laboratory synthesis of Annonaceous acetogenin mimic AA005

Yu, Bao-Bao; Yao, Zhu‐Jun

doi:10.1016/j.cclet.2020.06.007

Cited by 4 publications

(4 citation statements)

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“…A gram-scale laboratory synthesis of Annonaceous acetogenin mimic AA005 was reported by our group, [13] and its optical purity (dr, 97.3 : 2.7) was confirmed by a chiral HPLC analysis. AA005 was prepared with dimethyl sulfoxide (DMSO) as a solvent to form a 500 μM AA005 storage solution on cells and diluted to the corresponding concentrations with culture medium as the working solution, and the DMSO final concentration was 0.4% in all the cultures.…”

Section: Methodsmentioning

confidence: 84%

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Annonaceous Acetogenin Mimic AA005 Inhibits the Growth of TNBC MDA‐MB‐468 Cells by Altering Cell Energy Metabolism

Yuan

Chen

et al. 2022

ChemBioChem

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Triple‐negative breast cancer (TNBC) is a serious health issue for women worldwide and there is still no suitable treatment option. AA005, a structurally simplified mimic of natural Annonaceous acetogenins, presents outstanding properties with impressive cytotoxicity and cell‐type selective actions. The present study was aimed at evaluating the potential of AA005 as a therapeutic agent for TNBC. AA005 potently inhibited the growth of TNBC cells at 50 nM level. Inspired by the finding of the phosphatase and tensin homologue (PTEN) tumor suppressor, the effect of AA005 on aerobic glycolysis was investigated in TNBC MDA‐MB‐468 cells. A short‐term AA005 exposure markedly suppressed mitochondrial function in MDA‐MB‐468 cells, thus activating the aerobic glycolysis to lessen the risk of decreased ATP generation in mitochondria. Prolonging the incubation time of AA005 clearly weakened the aerobic glycolysis in the cells. This was in part attributed to the PI3K‐AKT pathway inactivation and subsequent declined glucose uptake. As a consequence, the energy supply was completely cut from the two major energy‐producing pathways. Further experiments showed that AA005 resulted in irreversible damage on cell activity including cell cycle and growth, inducing mitochondrial oxidative stress and ultimately leading to cell death. In addition, the in vivo therapeutic efficacy of AA005 was proved on 4T1 xenograft tumor mice model. Our data demonstrate that AA005 exhibited a great potential for future clinical applications in TNBC therapy.

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Section: Methodsmentioning

confidence: 84%

“…[12] Targeting the cellular energetics is an advantages channel for cancer care, including the unmanageable TNBC. In this paper, we studied the effect of Annonaceous acetogenins mimic AA005 [13] (Figure 1A) on cell energy metabolism of TNBC MDA-MB-468 cells.…”

Section: Introductionmentioning

confidence: 99%

Annonaceous Acetogenin Mimic AA005 Inhibits the Growth of TNBC MDA‐MB‐468 Cells by Altering Cell Energy Metabolism

Yuan

Chen

et al. 2022

ChemBioChem

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“…Following the same approach as described above for lineal ethers, Yu et al have recently synthesized at gram-scale a new and interesting derivative, based on bullatacin ( Figure 5 ), known as AA005, [ 80 ]. This Annona cherimola acetogenin mimic has been tested against human colon carcinoma cell line SW620 in vivo, and against different human cancer cell lines in vitro [ 81 ].…”

Section: Annona Cherimola Mill Acetogenin Derivativesmentioning

confidence: 99%

An Overview of the Chemical Characteristics, Bioactivity and Achievements Regarding the Therapeutic Usage of Acetogenins from Annona cherimola Mill.

et al. 2021

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Annona cherimola Mill., or the custard apple, is one of the species belonging to the Annonaceae family, is widely used in traditional medicine, and has been reported to be a valuable source of bioactive compounds. A unique class of secondary metabolites derived from this family are Annonaceous acetogenins, lipophilic polyketides considered to be amongst the most potent antitumor compounds. This review provides an overview of the chemical diversity, isolation procedures, bioactivity, modes of application and synthetic derivatives of acetogenins from A. cherimola Mill.

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“…Some paper reviews have highlighted the traditional medicinal uses, phytochemical and pharmacological studies, and toxicity of most Annonaceae species, which indicate the presence of bioactive compounds exhibiting antimicrobial, insecticide, antiparasitic, pesticide, vermicide, and cytotoxic properties, among others [ 3 , 4 ]. Annonaceae are significant from an economic point of view given the numerous ways of using their species, such as fruits in food and cooking, rich in lipids and carbohydrates, in addition to diterpenes, acetogenins, alkaloids, and essential oils, among the constituents of secondary metabolism with a more outstanding contribution to the biological activities already observed, and which have served as primary compounds in the production of new drugs [ 5 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Phytochemical Analysis of the Fruit Pulp Extracts from Annona crassiflora Mart. and Evaluation of Their Antioxidant and Antiproliferative Activities

Carvalho

Monteiro

Rocha

et al. 2022

Foods

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Annona crassiflora Mart., the marolo fruit of the Cerrado biome, is one of the most frequently consumed species from the Brazilian Midwest. This study aimed to evaluate the chemical composition and the antioxidant and cytotoxic properties of the fruit pulp of A. crassiflora collected at Chapada das Mesas, Maranhão, Brazil. The volatile concentrate was identified as mainly ethyl octanoate, ethyl hexanoate, and methyl octanoate. From the ethanol (LFP-E) and ethyl acetate (LFP-A) extracts were identified phenolic acids (p-coumaric, gallic, quinic, and ferulic), flavones and derivatives (apigenin, epicatechin, 2′-5-dimethoxyflavone, 3′,7-dimethoxy-3-hydroxyflavone, kaempferol-3-O-glucoside and 3-O-rutinoside, quercetin-3-O-glucoside, procyanidin B2, and rutin), aporphine alkaloids (xylopine, stephagine, and romucosine), and acetogenin (annonacin). For the LFP-E and LFP-A extracts, the total phenolic compound values were 15.89 and 33.16 mg GAE/g, the flavonoid compound content values were 2.53 and 70.55 mg QE/g, the DPPH radical scavenging activity showed EC50 values of 182.54 and 57.80 µg/mL, and the ABTS radical activity showed TEAC values of 94.66 and 192.61 µM TE/g. The LFP-E extract showed significant cytotoxicity and cell selectivity for the U251-glioma strain, presenting a GI50 value of 21.34 µg/mL, which is close to doxorubicin (11.68 µg/mL), the standard chemotherapeutic drug. The marolo fruit seems to be a promising source for developing innovative and healthy products for the food industry.

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A gram-scale laboratory synthesis of Annonaceous acetogenin mimic AA005

Cited by 4 publications

References 38 publications

Annonaceous Acetogenin Mimic AA005 Inhibits the Growth of TNBC MDA‐MB‐468 Cells by Altering Cell Energy Metabolism

Annonaceous Acetogenin Mimic AA005 Inhibits the Growth of TNBC MDA‐MB‐468 Cells by Altering Cell Energy Metabolism

An Overview of the Chemical Characteristics, Bioactivity and Achievements Regarding the Therapeutic Usage of Acetogenins from Annona cherimola Mill.

Phytochemical Analysis of the Fruit Pulp Extracts from Annona crassiflora Mart. and Evaluation of Their Antioxidant and Antiproliferative Activities

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