Design and synthesis of novel oridonin analogues as potent anticancer agents

Shen, Qing-Kun; Zheng-ai, Chen; Zhang, Hongjian; Li, Jiali; Liu, Chuan-Feng; Gong, Guo-Hua; Quan, Zhe‐Shan

doi:10.1080/14756366.2017.1419219

Cited by 17 publications

(7 citation statements)

References 26 publications

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“…An ent-kaurane diterpenoid isolated from Isodon rubescens, Oridonin (Ori) and its analogs exert anti-tumor potential in cancer cells (23–25). Besides, the mechanisms involved are mainly concentrated on autophagy and apoptosis (26, 27).…”

Section: Introductionmentioning

confidence: 99%

Oridonin Sensitizes Cisplatin-Induced Apoptosis via AMPK/Akt/mTOR-Dependent Autophagosome Accumulation in A549 Cells

et al. 2019

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AMPK-mediated autophagy and Akt/mTOR pathways play important roles in current cancer treatments. Oridonin (Ori), an ent-kaurane diterpenoid isolated from Isodon rubescens, exerts extensive anti-tumor potential and controversial effects on autophagy. In this study, we investigated the effect of Ori on the autophagy, apoptosis, and AMPK/Akt/mTOR pathways and determined whether Ori was related to the increased cisplatin sensitivity observed in A549 cells. First, we found that Ori suppressed Akt/mTOR, Bcl2 and autophagy flux with enhanced levels of Atg3, P62, and LC3II, which was also shown as the accumulation of autophagosomes. AMPK and pro-apoptotic proteins (caspase3, Bax, and PARP) were activated in Ori-treated cells. With the pretreatment of compound c (AMPK inhibitor), the activation of autophagosomes, apoptosis and the inhibition of Akt/mTOR pathways induced by Ori were all reversed. The Ori-activated apoptosis-related markers mentioned previously and the cell-killing effect were restrained by 3-MA (inhibitor of autophagosomes) treatment. Therefore, we hypothesized that the Ori-induced pro-apoptotic effect was mediated by AMPK/Akt/mTOR-dependent accumulation of impaired autophagosomes. Furthermore, Ori could increase the sensitivity of cisplatin through its increased cell-killing, autophagy-suppressing and apoptosis-inducing activities. In addition to sensitizing cisplatin, Ori also alleviated cisplatin-induced acute renal injury in vivo , manifested as depleted BUN, CRE, kidney index, and weight loss compared to the cisplatin group. In summary, apart from its protective effect on cisplatin-induced nephrotoxicity, Ori enhanced cisplatin sensitivity via its pro-apoptotic activity mediated by AMPK/Akt/mTOR-dependent autophagosome activation, which may be a potential therapeutic target for non-small cell lung cancer.

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Section: Introductionmentioning

confidence: 99%

Oridonin Sensitizes Cisplatin-Induced Apoptosis via AMPK/Akt/mTOR-Dependent Autophagosome Accumulation in A549 Cells

et al. 2019

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“…The cytotoxicity of EL, MEL and compounds 1–6 on two cancer cell lines was determined by MTT assay. 22 The cells were seeded in five-well plates (1 × 10 4 cells per well) and incubated at 37 °C for 24 h. The cells were then treated with EL, MEL, cisplatin and compounds 1–6 at different concentrations (0.1–100 μmol L −1 ). Cisplatin was used as the positive control.…”

Section: Methodsmentioning

confidence: 99%

“…9B). The structure-activity results revealed that the hydroxy-substituted compounds at C-20 (20 (S/R)-Rg 3 ) had the hemostatic activities, while Rk 1 , SFt 3 and Rg 5 with double bond at D20 (21) or D20 (22) played the anticoagulant activities. The anticoagulant activity of the MEL increased due to increases in the concentrations of Rk 1 , Rg 5 , and SFt 3 .…”

Section: The Anticoagulant Effect Of the Transformation Products In Vmentioning

confidence: 99%

Converting ginsenosides from stems and leaves of Panax notoginseng by microwave processing and improving their anticoagulant and anticancer activities

Liu

Guo

et al. 2018

RSC Adv.

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“…Nonetheless, Shen et al (2018) demonstrated that α, β-unsaturated ketones can be targets for structural modifications to achieve promising derivatives. Shen’s group synthesized oridonin derivatives with substituted benzene moieties at the C17 position, and compound 16 (listed in Table 3 ) proved to be the most potent with an IC 50 value of 1.05 μM against the HCT-116 cell line.…”

Section: Oridonin Derivatives: Potential Agents In Anticancer Therapymentioning

confidence: 99%

Recent advances in oridonin derivatives with anticancer activity

2023

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Cancer is a leading cause of mortality responsible for an estimated 10 million deaths worldwide in 2020, and its incidence has been rapidly growing over the last decades. Population growth and aging, as well as high systemic toxicity and chemoresistance associated with conventional anticancer therapies reflect these high levels of incidence and mortality. Thus, efforts have been made to search for novel anticancer drugs with fewer side effects and greater therapeutic effectiveness. Nature continues to be the main source of biologically active lead compounds, and diterpenoids are considered one of the most important families since many have been reported to possess anticancer properties. Oridonin is an ent-kaurane tetracyclic diterpenoid isolated from Rabdosia rubescens and has been a target of extensive research over the last few years. It displays a broad range of biological effects including neuroprotective, anti-inflammatory, and anticancer activity against a variety of tumor cells. Several structural modifications on the oridonin and biological evaluation of its derivatives have been performed, creating a library of compounds with improved pharmacological activities. This mini-review aims to highlight the recent advances in oridonin derivatives as potential anticancer drugs, while succinctly exploring their proposed mechanisms of action. To wind up, future research perspectives in this field are also disclosed.

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Design and synthesis of novel oridonin analogues as potent anticancer agents

Cited by 17 publications

References 26 publications

Oridonin Sensitizes Cisplatin-Induced Apoptosis via AMPK/Akt/mTOR-Dependent Autophagosome Accumulation in A549 Cells

Oridonin Sensitizes Cisplatin-Induced Apoptosis via AMPK/Akt/mTOR-Dependent Autophagosome Accumulation in A549 Cells

Converting ginsenosides from stems and leaves of Panax notoginseng by microwave processing and improving their anticoagulant and anticancer activities

Recent advances in oridonin derivatives with anticancer activity

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