Piperazine tethered bergenin heterocyclic hybrids: design, synthesis, anticancer activity, and molecular docking studies

Rao, Banoth Venkateswara; Kumar, Pankaj; Ramalingam, Vaikundamoorthy; Karthik, G.; Andugulapati, Sai Balaji; Babu, K. Suresh

doi:10.1039/d2md00116k

Cited by 8 publications

(3 citation statements)

References 30 publications

(36 reference statements)

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“…Targeting ubiquitination of Mcl-1 is allowed for rapidly eliminating proteins and triggering cell death while responding to various cellular events [ 37 ]. Environmental cadmium exposure leads to placental apoptosis and fetal growth restriction through Parkin-induced degradation of Mcl-1 ubiquitination during gestation [ 38 ]. Inhibition of BMI-1 also leads to DUB3-dependent Mcl-1 degradation, resulting in enhanced apoptosis of cancer cells [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Targeting Mcl-1 Degradation by Bergenin Inhibits Tumorigenesis of Colorectal Cancer Cells

Gan

Han

et al. 2023

Pharmaceuticals

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Myeloid leukemia 1 (Mcl-1) is frequently overexpressed in human malignancies and emerged as a promising drug target. In this study, we verified the inhibitory effect of bergenin on colorectal cancer cells both in vivo and in vitro. In an in vitro setting, bergenin significantly reduced the viability and colony formation and promoted apoptosis of CRC cells dose-dependently. Bergenin decreased the activity of Akt/GSK3β signaling and enhanced the interaction between FBW7 and Mcl-1, which eventually induced Mcl-1 ubiquitination and degradation. Using the HA-Ub K48R mutant, we demonstrated that bergenin promotes Mcl-1 K48-linked polyubiquitination and degradation. In vivo studies showed that bergenin significantly reduced tumor size and weight without toxicity to vital organs in mice. Overall, our results support the role of bergenin in inhibiting CRC cells via inducing Mcl-1 destruction, suggesting that targeting Mcl-1 ubiquitination could be an alternative strategy for antitumor therapy.

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Section: Discussionmentioning

confidence: 99%

Targeting Mcl-1 Degradation by Bergenin Inhibits Tumorigenesis of Colorectal Cancer Cells

Gan

Han

et al. 2023

Pharmaceuticals

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“…But other protein targets are implicated in the mechanism of action. Previous studies also suggested the binding of bergenin to the proteins NLRP3 (NOD-like receptor family-pyrin domain containing 3) inflammasome [129], antiapoptotic protein B-Cell Lymphoma 2 (Bcl-2) [130], enzyme galectin-3 [131] and several other proteins [132][133][134][135].…”

Section: Polyphenols and Flavonoidsmentioning

confidence: 94%

Traditional Uses, Pharmacology and Phytochemistry of the Medicinal Plant Flueggea virosa (Roxb. ex Willd.) Royle

Bailly

2024

Future Pharmacology

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The white berry bush, officially Flueggea virosa (Roxb. ex Willd.) Royle is a medicinal plant distributed throughout tropical areas and traditionally used in Africa, India and China. Root decoctions are used to treat abdominal pain, whereas extracts from the aerial parts serve to treat liver and urinary diseases, inflammatory pathologies and diabetes, among other pathologies. Plant extracts have revealed antiparasitic, antimicrobial, antiepilepsy, antidiabetic, anticancer and analgesic effects. Three main categories of phytochemicals were isolated from F. virosa: polyphenols, with the lead product bergenin; terpenoids, such as the flueggenoids and related podocarpane-type diterpenoids; and many alkaloids derived from securinine and norsecurinine. A remarkable feature of S. virosa is the production of norsecurinine oligomers, including macromolecular tetramers and pentamers, such as fluevirosinines. The most potent anticancer alkaloid in the family is the dimeric indolizidine flueggine B, which was identified as a potential binder to α/β-tubulin dimer, which is a known target for securinine. This review highlights the diversity of phytochemicals identified from S. virosa and the potential therapeutic benefits of dimeric alkaloids. Studies are encouraged to further investigate the therapeutic properties of the lead compounds but also define and finesse the nutritional profile of the edible fruit.

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“…Annexin V-FITC apoptosis detection kit was used to determine the effect of compounds on CAL-27 cells as described previously (Venkateswara Rao et al 2022). Initially, the CAL-27 cells in the density of 5×10 3 cells were seeded in 6-well plate and incubated for overnight at 37 °C in 5% CO 2 .…”

Section: Apoptosis Analysismentioning

confidence: 99%

Synthesis of novel thiazoles bearing lupeol derivatives as potent anticancer and anti-inflammatory agents

Narendar

Rao

Tirunavalli

et al. 2023

Natural Product Research

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Lupeol is one of the most important metabolite in the class of terpenoids and possess excellent anticancer, anti-inflammatory, anti-diabetic activities etc. In the present study, the different thiazoles and oxazoles bearing lupeol derivatives were prepared to enhance their biological activity. Initially, the in vitro cytotoxic activity results showed that the synthesized lupeol derivatives (9a-9j and 10a-10e) showed significant activity against various cancer cells and the compounds 9h and 10b exhibited excellent activity against CAL27 cells. Further, these compounds 9h and 10b arrest the cell cycle at S phase and induce the late apoptosis in CAL27 cells by downregulating the BcL2 and vimentin expression and upregulating the Bax gene expression. Moreover, the lupeol derivatives showed dose-dependent anti-inflammatory activity by inhibiting the secretion of IL-6 cytokines in LPS-induced Raw 264.7 cells. Together, these results clearly indicated that the thiazoles and oxazoles bearing lupeol derivatives can used as chemotherapeutic drugs against cancer and inflammatory diseases.

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Piperazine tethered bergenin heterocyclic hybrids: design, synthesis, anticancer activity, and molecular docking studies

Abstract: Novel piperazine-linked bergenin derivatives were synthesized and the compounds 5a, 5c, 10f, and 13o showed excellent cytotoxic activity. These compounds arrest the cell cycle and induce apoptosis by regulating the Bax/BcL2 expression.

Cited by 8 publications

References 30 publications

Targeting Mcl-1 Degradation by Bergenin Inhibits Tumorigenesis of Colorectal Cancer Cells

Targeting Mcl-1 Degradation by Bergenin Inhibits Tumorigenesis of Colorectal Cancer Cells

Traditional Uses, Pharmacology and Phytochemistry of the Medicinal Plant Flueggea virosa (Roxb. ex Willd.) Royle

Synthesis of novel thiazoles bearing lupeol derivatives as potent anticancer and anti-inflammatory agents

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