An alternative approach to the synthesis of anticancer molecule spirobrassinin and its 2′-amino analogues

Budovská, Mariana; Tischlerová, Viera; Mojžiš, Ján; Kozlov, Oleksandr; Gondová, Taťána

doi:10.1007/s00706-019-02528-x

Cited by 15 publications

(5 citation statements)

References 32 publications

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“…Additionally, it demonstrated notably lower toxicity compared to cisplatin on HUVEC cells. These results indicate the importance of the CF3 group for enhanced biological activity [91].…”

Section: Antiproliferative Effects Of Synthetic Analogues Of Indole P...mentioning

confidence: 72%

Anticancer Potential of Indole Phytoalexins and Their Analogues

Zigová,

Michalková,

Mojžiš

2024

Molecules

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Indole phytoalexins, found in economically significant Cruciferae family plants, are synthesized in response to pathogen attacks or stress, serving as crucial components of plant defense mechanisms against bacterial and fungal infections. Furthermore, recent research indicates that these compounds hold promise for improving human health, particularly in terms of potential anticancer effects that have been observed in various studies. Since our last comprehensive overview in 2016 focusing on the antiproliferative effects of these substances, brassinin and camalexin have been the most extensively studied. This review analyses the multifaceted pharmacological effects of brassinin and camalexin, highlighting their anticancer potential. In this article, we also provide an overview of the antiproliferative activity of new synthetic analogs of indole phytoalexins, which were synthesized and tested at our university with the aim of enhancing efficacy compared to the parent compound.

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“…Additionally, it demonstrated notably lower toxicity compared to cisplatin on HUVEC cells. These results indicate the importance of the CF3 group for enhanced biological activity [91].…”

Section: Antiproliferative Effects Of Synthetic Analogues Of Indole P...mentioning

confidence: 72%

Anticancer Potential of Indole Phytoalexins and Their Analogues

Zigová,

Michalková,

Mojžiš

2024

Molecules

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“…Figure 1 depicts diverse spirooxindole frameworks sourced from nature, showcasing potent anti-cancer activity ( Yu et al, 2015 ). Of particular note is Spirobrassinin, an oxindole alkaloid renowned for its robust anti-tumor properties ( Budovská et al, 2020 ), along with spindomycins A and B, identified as potential inhibitors of the tyrosine kinase Bcr-Abl ( Guo et al, 2014 ). Spirotryprostatins A and B exhibit noteworthy inhibitory effects against mouse breast cancer, specifically targeting tsFT210 ( Ding et al, 2005 ; Al-Rashood et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Exploring pyrrolidinyl-spirooxindole natural products as promising platforms for the synthesis of novel spirooxindoles as EGFR/CDK2 inhibitors for halting breast cancer cells

Nafie,

Al-Majid,

Ali

et al. 2024

Front. Chem.

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Cancer represents a global challenge, and the pursuit of developing new cancer treatments that are potent, safe, less prone to drug resistance, and associated with fewer side effects poses a significant challenge in cancer research and drug discovery. Drawing inspiration from pyrrolidinyl-spirooxindole natural products, a novel series of spirooxindoles has been synthesized through a one-pot three-component reaction, involving a [3 + 2] cycloaddition reaction. The cytotoxicity against breast cancer cells (MCF-7 and MDA-MB-231) and safety profile against WISH cells of the newly developed library were assessed using the MTT assay. Compounds 5l and 5o exhibited notable cytotoxicity against MCF-7 cells (IC50 = 3.4 and 4.12 μM, respectively) and MDA-MB-231 cells (IC50 = 8.45 and 4.32 μM, respectively) compared to Erlotinib. Conversely, compounds 5a-f displayed promising cytotoxicity against MCF-7 cells with IC50 values range (IC50 = 5.87–18.5 μM) with selective activity against MDA-MB-231 cancer cells. Compound 5g demonstrated the highest cytotoxicity (IC50 = 2.8 μM) among the tested compounds. Additionally, compounds 5g, 5l, and 5n were found to be safe (non-cytotoxic) against WISH cells with higher IC50 values ranging from 39.33 to 47.2 μM. Compounds 5g, 5l, and 5n underwent testing for their inhibitory effects against EGFR and CDK-2. Remarkably, they demonstrated potent EGFR inhibition, with IC50 values of 0.026, 0.067, and 0.04 μM and inhibition percentages of 92.6%, 89.8%, and 91.2%, respectively, when compared to Erlotinib (IC50 = 0.03 μM, 95.4%). Furthermore, these compounds exhibited potent CDK-2 inhibition, with IC50 values of 0.301, 0.345, and 0.557 μM and inhibition percentages of 91.9%, 89.4%, and 88.7%, respectively, in contrast to Roscovitine (IC50 = 0.556 μM, 92.1%). RT-PCR analysis was performed on both untreated and 5g-treated MCF-7 cells to confirm apoptotic cell death. Treatment with 5g increased the gene expression of pro-apoptotic genes P53, Bax, caspases 3, 8, and 9 with notable fold changes while decreasing the expression of the anti-apoptotic gene Bcl-2. Molecular docking and dynamic simulations (100 ns simulation using AMBER22) were conducted to investigate the binding mode of the most potent candidates, namely, 5g, 5l, and 5n, within the active sites of EGFR and CDK-2.

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“…Hortensis (Cruciferae) 24 . The total synthesis and anticancer properties of this compound have been described 25 . Mitraphylline is an oxindole derivative originally isolated from the leaves of Mitragyna speciosa 26 .…”

Section: Introductionmentioning

confidence: 99%

An evaluation of spirooxindoles as blocking agents of SARS-CoV-2 spike/ACE2 fusion and M pro inhibitory agents: Synthesis, biological evaluation and computational analysis

Ehinak,

Lobe,

Simoben

et al. 2024

Preprint

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Both tetrahydroisoquinolines (THIQs) and oxindoles (OXs) display a broad range of biological activities, including antiviral activity. They are, therefore, recognized as privileged scaffolds in drug discovery. Here, we describe the synthesis of spirofused tetrahydroisoquinoline–oxindole hybrids (spirooxindoles) and their evaluation as potential blocking agents of both SARS-CoV-2 spike/ACE fusion and inhibitors of the main protease (Mpro). The most active synthesized compound showed a 50% inhibitory concentration (IC50) of 3.6 µM against SARS-CoV-2 spike/ACE fusion. None of the tested compounds was shown to be active against Mpro. The most active compound possesses a bulky naphthyl group, which addresses voluminous hydrophobic regions of the ACE2 binding site and interacts with the hydrophobic residues of the target; this finding agrees with previous studies revealing that bulky compounds block spike/ACE2 fusion, e.g., the natural product hopeaphenol. Therefore, spirooxindoles may provide useful leads in the search for SARS-CoV-2 spike/ACE fusion blocking agents.

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An alternative approach to the synthesis of anticancer molecule spirobrassinin and its 2′-amino analogues

Cited by 15 publications

References 32 publications

Anticancer Potential of Indole Phytoalexins and Their Analogues

Anticancer Potential of Indole Phytoalexins and Their Analogues

Exploring pyrrolidinyl-spirooxindole natural products as promising platforms for the synthesis of novel spirooxindoles as EGFR/CDK2 inhibitors for halting breast cancer cells

An evaluation of spirooxindoles as blocking agents of SARS-CoV-2 spike/ACE2 fusion and M pro inhibitory agents: Synthesis, biological evaluation and computational analysis

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