Synthesis of Novel ent-Kaurane-Type Diterpenoid Derivatives Effective for Highly Aggressive Tumor Cells

Hu, Yu; Li, Xiaonian; Ma, Ze-Jin; Puno, Pema‐Tenzin; Zhao, Yong; Zhao, Yan; Xiao, Ye-Zhi; Zhang, Wei; Liu, Jing‐Ping

doi:10.3390/molecules23123216

Cited by 5 publications

(6 citation statements)

References 13 publications

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“…A silylation reaction of compound 6 was used to produce compound 7 . Deprotonation of compound 7 with Lithium bis(trimethylsilyl)amide (LiHMDS), followed by reaction with compound 8 10 led to product 9 as the major product, along with the isomer 10 in 86% combined yield (dr =9:1) (Scheme 1). Compound 9 is a crystal that was confirmed by NMR spectral and X-ray crystallographic analysis (Figure 3), its epimer compound 10 is a powder.…”

Section: Resultsmentioning

confidence: 99%

<p>Synthesis and antitumor evaluation of neolaxiflorin B inspired compounds</p>

Liu

Xiao

et al. 2019

DDDT

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BackgroundNeolaxiflorin B is derived from ent-kaurane like laxiflorin J and eriocalyxin B with a relatively low potency as an antitumor agent. During preliminary structure–activity relationship studies, the α,β-unsaturated ketone (enone) system is an important active group.MethodsSeven neolaxiflorin B derivatives containing α,β-unsaturated ketone moieties were synthesized. In vitro, activity was evaluated against three human tumor cell lines and a rat myogenic cell line (HepG2, NSCLC-H292, SNU-1040, and L6, respectively) by MTT assay.ResultsCompound 15 appeared a promising antitumor lead due to its cytotoxic potency and relatively high selectivity, with an SI value of 13.14. Flow cytometry analysis was conducted to show that NSCLC-H292 cells were blocked in the G0/G1 phase in the presence of compound 15, thus inhibiting the proliferation of tumor cells.ConclusionThis study has revealed that compound 15 is a promising antitumor lead due to the cytotoxic potencies and the high selectivity it displayed when compared to natural counterparts.

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Section: Resultsmentioning

confidence: 99%

<p>Synthesis and antitumor evaluation of neolaxiflorin B inspired compounds</p>

Liu

Xiao

et al. 2019

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“…The ent-kaurane diterpenoids were previously isolated from the leaves of the plant C tonkinensis. [10][11][12][13][14][15] The purification and structure identification of the compounds were performed at the Institute of Natural Products Chemistry-Vietnam Academy of Science and Technology. The purity of the compounds was determined as ≥97% by high-performance liquid chromatography.…”

Section: Plant Materials Preparationmentioning

confidence: 99%

“…[9][10][11][12] Of the various ent-kaurane diterpenoids from C tonkinensis described so far in the literature, only a few compounds have been studied against the NSCLC model; therefore, the mechanism by which they affect this cell line is still scarcely explored. 10,[13][14][15] In NSCLC, the phosphatidylinositol-3-kinase (PI3K) pathway has been heavily implicated in both tumorigenesis and the progression of disease. 16 There are various genomic episodes that could distort the normal regulation of the pathway such as mutation, amplification, and displacement.…”

Section: Introductionmentioning

confidence: 99%

Identification of Ent-Kaurane Diterpenoid Compounds as Potential Inhibitors of the PI3K Pathway in Nonsmall Cell Lung Cancer Through Molecular Docking Simulations

Minh

Van

Toàn

et al. 2021

Natural Product Communications

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Annual mortality of 8.2 million could be attributable to cancer globally, posing a serious health issue; particularly, the high number of nonsmall cell lung cancer (NSCLC) diagnosed cases in recent years highlight the need for development in anticancer agents. In NSCLC, a number of specific inhibitors of phosphatidylinositol-3-kinase (PI3K), Protein kinase B (AKT), and mammalian target of rapamycin are currently under development; however, the early evidence has yielded disappointing results. Ent-kaurane diterpenoid compounds from Cronton tonkinensis have been investigated for several bioactivities such as antibacterial, cytotoxic activity, and so on;; however, lung cancer is not yet studied. In this study, we conducted a molecular docking study of 7 ent-kaurane diterpenoids from C tonkinensis against PI3K targeted anticancer therapies; furthermore, their cytotoxicity effects against A549 lung cancer cells were also evaluated. Obtained results indicated that compounds 7, 6, 2, and 1 exhibited significant inhibitory results in comparison to the reference drug oxaliplatin which suggests further in vitro assay for drug development.

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“…In case of Parkinson's disease, inflammation in substantia nigra happens due to overproduction of inflammatory factors leading to the dysfunction of dopaminergic neurons. 61 EriB has competency to protect the dopaminergic neurons via prohibiting the production of proinflammatory cytokines and selectively modulating MPP + induced microglia activation via targeting NF-κB. 62 EriB inhibits NF-κB activity in a dose-dependent way and reduces inflammation in the damaged tissues.…”

Section: Anti-inflammatory Activitymentioning

confidence: 99%

Eriocalyxin B Biological Activity: A Review on Its Mechanism of Action

Riaz

Saleem

Hussain

et al. 2019

Natural Product Communications

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Natural products, a rich source of bioactive chemical compounds, have served humans as a safer drug of choice since times. Eriocalyxin B, an ent-Kaurene diterpenoid, has been extracted from a traditional Chinese herb Isodon eriocalyx. Experimental data support the anticancer and anti-inflammatory activities of EriB. This natural entity exhibits anticancer effects against breast, pancreatic, leukemia, ovarian, lung, bladder, and colorectal cancer. EriB has capability to inhibit the proliferation of cancer cells by prompting apoptosis, arresting cell cycle, and modulating cell signaling pathways. The regulation of signaling pathways in cancerous cells by EriB involves the modulation of various apoptosis-related factors (Bak, Bax, caspases, XIAP, survivin, and Beclin-1), transcriptional factors (nuclear factor kappa B [NF-κB], STAT3, Janus-activated kinase 2, Notch, AP-1, and lκBα), enzymes (cyclooxygenase 2, matrix metalloproteinase 2 [MMP-2], MMP-9, and poly (ADP-ribose) polymerase), cytokines, and protein kinases (mitogen-activated protein kinase and ERK1/2). This review proposes that EriB supplies a novel opportunity for the cure of cancer but supplementary investigations along with preclinical trials are obligatory to effectively figure out its biological and pharmacological applications.

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Synthesis of Novel ent-Kaurane-Type Diterpenoid Derivatives Effective for Highly Aggressive Tumor Cells

Cited by 5 publications

References 13 publications

<p>Synthesis and antitumor evaluation of neolaxiflorin B inspired compounds</p>

<p>Synthesis and antitumor evaluation of neolaxiflorin B inspired compounds</p>

Identification of Ent-Kaurane Diterpenoid Compounds as Potential Inhibitors of the PI3K Pathway in Nonsmall Cell Lung Cancer Through Molecular Docking Simulations

Eriocalyxin B Biological Activity: A Review on Its Mechanism of Action

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