Anticancer activity of bisindole alkaloids derived from natural sources and synthetic bisindole hybrids

Zhang, Yue; Hu, Chunhong

doi:10.1002/ardp.202000092

Cited by 26 publications

(11 citation statements)

References 88 publications

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“…Therefore, the researcher main goal is to develop promising cancer drugs addressed to enhance apoptotic inhibitors including Bcl‐2 family proteins and other substrates. BrDIMEA , like other marine bisindole alkaloids (Lunagariya et al, 2019; Zhang & Hu, 2020), can be considered a strong apoptotic agent in various cell models, including U937 cells, where it induces apoptosis following both extrinsic and intrinsic pathways and by involving the Bcl‐2 protein family (Salucci et al, 2018). Salucci and collaborators demonstrated the ability of this chemical alkaloid to up‐regulate bax and to inactivate Bcl‐2 and Bcl‐xL (Salucci et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Morpho‐functional analyses reveal that changes in the chemical structure of a marine bisindole alkaloid alter the cytotoxic effect of its derivatives

Burattini

Battistelli

Verboni

et al. 2022

Microscopy Res & Technique

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2,2-bis(6-bromo-1H-indol-3-yl) ethanamine, a marine bisindole alkaloid, showed anticancer property in several tumor cell lines thanks to the presence of a 3,3 0diindolylmethane scaffold. Here, the modifications in its chemical structure into alkaloid-like derivatives, have been evaluated, to investigate changes in its biological activities. Three derivatives have been considered and their potential apoptotic action has been evaluated through morpho-functional analyses in a human cancer cell line. Apoptosis appears strongly decreased in the derivatives without the bromine atoms (1) and in those where the bromine atoms have been substituted with fluorine atoms (2). On the contrary, the methylation of indole NH (3) does not alter the alkaloid apoptotic activity that occurs through mitochondria involvement supported by cardiolipin peroxidation and dysfunctional mitochondria presence. This manuscript highlights the alkaloid derivative cytotoxic effect, which is strictly correlated to the presence of N-methylated bisindole alkaloid and bromine atoms, conditions which assure to maintain the pro-apoptotic activity. Since molecular therapies, by targeting mitochondria pathways, have shown positive outcomes against several cancer cells, the alkaloid with bisindole methylated scaffold and the two bromine atoms can be considered a promising candidate to develop new derivatives with strong anticancer property.anticancer activity, apoptotic cell death, marine alkaloids, mitochondria damage, U937 cell line Research Highlights• 2,2-bis(6-bromo-1H-indol-3-yl) ethanamine is an alkaloid known for its anticancer properties.• Morpho-functional analyses evaluated cytotoxicity of its synthetic derivatives in tumor cells.• Anticancer properties depend on the presence of bisindole scaffold and the two bromine units.Marine bisindole alkaloids showed significant cytotoxicity, antineoplastic and antimicrobial properties (Kamel et al., 2020; Veale & Davies-Coleman, 2014). In particular, 2,2-bis(6-bromo-3-indolyl) ethanamine (BrDIMEA), extracted from the Californian tunicate Didemnum candidum and the New Caledonian sponge Orina (Salucci et al., 2018), is a strong cytotoxic agent and its anticancer

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Section: Discussionmentioning

confidence: 99%

Morpho‐functional analyses reveal that changes in the chemical structure of a marine bisindole alkaloid alter the cytotoxic effect of its derivatives

Burattini

Battistelli

Verboni

et al. 2022

Microscopy Res & Technique

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“…They are found from natural and synthetic sources. In addition, the derivatives of indoles have structural diversity and various therapeutic properties [90].…”

Section: Indolesmentioning

confidence: 99%

The Role of Intestinal Flora in Anti-Tumor Antibiotic Therapy

Ye¹,

Wang²,

Lin³

et al. 2022

Front. Biosci. (Landmark Ed)

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Anti-tumor antibiotics are chemical substances produced by micro-organisms to control cancer development. Some of the currently used cancer treatment regimens are anti-tumor antibiotics. However, many studies have demonstrated that anti-tumor antibiotics may have adverse effects on normal cells. This calls for development of strategies to alleviate these negative effects and improve cancer treatment. Recent studies have suggested that the efficacy of anti-tumor antibiotics may be affected by intestinal microbiota. For instance, intestinal microbiota can alleviate the negative effects of antibiotic treatment and regulate the tumor immune micro-environment. In this way, anti-tumor antibiotics can improve tumor control. However, the specific mechanisms need to be further explored. This review discusses the effect of intestinal flora on anti-tumor antibiotic therapy and summarizes the specific mechanisms by which antibiotics inhibit harmful intestinal micro-organisms and promote efficacy of probiotics, which may improve the control of neoplasm development and growth.

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Section: Indole Dimersmentioning

confidence: 99%

“…Moreover, several indole dimers that are represented by vincristine and vinblastine have already been applied in clinical practice, revealing the potential of indole dimers in the discovery of new drugs. [25,26] Many indole dimers are secondary metabolites widely distributed in nature and are an important source of anti-MRSA lead hits. Dragmacidin G (1, minimal inhibitory concentration [MIC]: 0.62 µg/ml; Figure 2), a pyrazine-tethered indole dimer, derived from a deep-water sponge of the genus Spongosorites, exhibited an excellent activity against S. aureus and MRSA, and the antibacterial activity was 5 to >80 times superior to that of chloramphenicol (MIC: 6.2 and 3.1 µg/ml) and methicillin (MIC: 3.1 and >50 µg/ml).…”

Section: Indole Dimersmentioning

confidence: 99%

Recent advances in indole dimers and hybrids with antibacterial activity against methicillin‐resistant Staphylococcus aureus

Meng

Hou

Shang

et al. 2020

Archiv der Pharmazie

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Methicillin‐resistant Staphylococcus aureus (MRSA), one of the major and most dangerous pathogens in humans, is a causative agent of severe pandemic of mainly skin and soft tissue and occasionally fatal infections. Therefore, it is imperative to develop potent and novel anti‐MRSA agents. Indole derivatives could act against diverse enzymes and receptors in bacteria, occupying a salient place in the development of novel antibacterial agents. Dimerization and hybridization are common strategies to discover new drugs, and a number of indole dimers and hybrids possess potential antibacterial activity against a panel of clinically important pathogens including MRSA. Accordingly, indole dimers and hybrids are privileged scaffolds for the discovery of novel anti‐MRSA agents. This review outlines the recent development of indole dimers and hybrids with a potential activity against MRSA, covering articles published between 2010 and 2020. The structure–activity relationship and the mechanism of action are also discussed to facilitate further rational design of more effective candidates.

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Anticancer activity of bisindole alkaloids derived from natural sources and synthetic bisindole hybrids

Cited by 26 publications

References 88 publications

Morpho‐functional analyses reveal that changes in the chemical structure of a marine bisindole alkaloid alter the cytotoxic effect of its derivatives

Morpho‐functional analyses reveal that changes in the chemical structure of a marine bisindole alkaloid alter the cytotoxic effect of its derivatives

The Role of Intestinal Flora in Anti-Tumor Antibiotic Therapy

Recent advances in indole dimers and hybrids with antibacterial activity against methicillin‐resistant Staphylococcus aureus

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