Novel Lycorine Derivatives as Anticancer Agents: Synthesis and In Vitro Biological Evaluation

Wang, Peng; Yuan, Hui-Hui; Zhang, Xue; Li, Yunping; Shang, Luqing; Yin, Zheng

doi:10.3390/molecules19022469

Cited by 32 publications

(22 citation statements)

References 19 publications

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“…The lycorine ( 2 ) we used for subsequent derivation was obtained as a hydrochloride salt ( 1 ), which was commercially available, more stable and much less expensive. Compounds 2 – 5a , 8 , 9 , 10 , 12 , 14 and 15 (Scheme S1) were prepared according to the procedures reported previously. Compounds 5 – 7 (Scheme ), 11 (Scheme ), 13 (Scheme ), 16 and 17 (Scheme ) were prepared using our methods.…”

Section: Resultsmentioning

confidence: 99%

Leveraging botanical resources for crop protection: the isolation, bioactivity and structure–activity relationships of lycoris alkaloids

Wang

Liu

et al. 2018

Pest Management Science

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Section: Resultsmentioning

confidence: 99%

Leveraging botanical resources for crop protection: the isolation, bioactivity and structure–activity relationships of lycoris alkaloids

Wang

Liu

et al. 2018

Pest Management Science

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“…The initial aim of the resent study was to verify the inhibitory effect of lycorine derivatives on enterovirus. Rapid phenotype screening was performed using a total of 26 previously synthesized lycorine derivatives (33,36) to assay the inhibitory activity of these molecules against EV71-GFP ( Table 1). Most of the tested compounds did not exhibit an anti-EV71 effect at a concentration of 40 M, with two significant exceptions: treatment with compounds 18 (1acetyllycorine) ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Lycorine derivatives and reagents. Lycorine derivatives were synthesized by our group (Table 1) (33,36). Stock solutions at a concentration of 10 mM were prepared in distilled water with dimethyl sulfoxide (DMSO) and diluted in DMEM with 10% FBS to different concentrations before use.…”

Section: Methodsmentioning

confidence: 99%

A Conserved Inhibitory Mechanism of a Lycorine Derivative against Enterovirus and Hepatitis C Virus

Guo

Wang

Cao

et al. 2016

Antimicrob Agents Chemother

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f Enterovirus 71 (EV71) (Picornaviridae family) and hepatitis C virus (HCV) (Flaviviridae family) are the causative agents of human hand, foot, and mouth disease (HFMD) and hepatitis C, resulting in a severe pandemic involving millions of infections in the Asia-Pacific region and worldwide. The great impact of EV71 and HCV on public health highlights the need to further our understanding of the biology of these two viruses and develop effective therapeutic antivirals. Here, we evaluated a total of 32 lycorine derivatives and demonstrated that 1-acetyllycorine suppressed the proliferation of multiple strains of EV71 in various cells. The results of the drug resistance analysis revealed that 1-acetyllycorine targeted a phenylalanine (F76) in EV71 2A protease (2A pro ) to stabilize the conformation of a unique zinc finger. Most interestingly, the zinc binding site in EV71 2A pro is the exclusive homolog of HCV NS3 among all viruses. Further analysis revealed that 1-acetyllycorine also inhibits HCV with high efficacy, and the mutation on R118 in HCV NS3, which corresponds to F76 in EV71 2A pro , confers the resistance of HCV to 1-acetyllycorine. These results revealed a conserved mechanism of 1-acetyllycorine against EV71 and HCV through targeting viral proteases. We also documented the significant synergistic anti-EV71 and anti-HCV effects of 1-acetyllycorine with reported inhibitors, supporting potential combination therapy for the treatment of EV71 and HCV infections. E nterovirus 71 (EV71) is one of the major etiological agents of human hand, foot, and mouth disease (HFMD) in the AsiaPacific region. Particularly, young children and immunodeficient populations are more susceptible to EV71 infection. EV71 infection results in severe aseptic meningitis, encephalitis, myocarditis, acute flaccid paralysis, and pulmonary edema, which lead to high fatality rates (1, 2). Chronic infection with hepatitis C virus (HCV) affects 180 million people worldwide, and 350,000 people die each year due to HCV-related complications (3). Hepatitis C not only affects the liver function but also induces liver fibrosis and cirrhosis, eventually leading to liver cancer (4).Both EV71 and HCV are positive-sense single-stranded RNA (ϩssRNA) viruses. EV71 is a member of the Enterovirus genus within the Picornaviridae family (5-7). The genome of EV71 encodes a polyprotein that is cleaved through viral proteases to generate four structural proteins (VP1 to VP4) required for viral capsid formation and seven nonstructural proteins (2A pro , 2B, 2C, 3A, 3B, 3C pro , and 3D pol ) for viral replication (8-10). HCV is a member of the Hepacivirus genus in the Flaviviridae family. The translated polyprotein of HCV is further processed into the structural proteins, including core protein and envelope glycoproteins E1 and E2; the nonstructural proteins are processed into NS2, NS3, NS4A, NS4B, NS5A, and NS5B (11).The successful replication of most viruses depends on the correct proteolytic processing of polyproteins. EV71 employs two viral proteases: 2A ...

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“…However, chemotherapy and radiotherapy usually lead to serious adverse effects, such as impairment of the hematopoietic and immune systems [26]. With the rapid development of traditional Chinese medicine with modern medical technologies in the last several decades, numerous studies have found that E. fischeriana Steud [27,28], norcantharidin [29], lycorine [30], curcumin [31], and other plant products have significant anti-tumor activities, including the inhibition of tumor cell growth and metastasis. In addition, most traditional Chinese medicines have significantly fewer adverse effects than chemotherapy, but with comparable therapeutic effects [32].…”

Section: Discussionmentioning

confidence: 99%

Jolkinolide A and Jolkinolide B Inhibit Proliferation of A549 Cells and Activity of Human Umbilical Vein Endothelial Cells

et al. 2017

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BackgroundJolkinolide A (JA) and Jolkinolide B (JB) are diterpenoids extracted from the roots of Euphorbia fischeriana Steud and have been shown to have anti-tumor activity. However, their effects on the ability of tumor cells to invade blood vessels and metastasize remain largely unknown. Investigations into the effects of JA and JB on the angiogenesis of tumor tissues may facilitate the identification of new natural drugs with anti-tumor growth and metastasis activities.Material/MethodsWe used different concentrations of JA and JB (20 μg/ml, 40 μg/ml, 60 μg/ml, 80 μg/ml, and 100 μg/ml) to stimulate A549 cells and then studied the effects on the growth and metastasis of lung cancers. In addition, we used conditional media from A549 cells (A549-CM) stimulated by either JA or JB in different concentrations to culture human umbilical vein endothelial cells (HUVECs).ResultsWe found that both JA and JB significantly inhibited the Akt-STAT3-mTOR signaling pathway and reduced the expression of VEGF in A549 cells, but JB exhibited more significant inhibitory effects than JA. The JB-stimulated A549 cell conditional media had a greater inhibitory effect on the proliferation and migration of HUVECs than did the conditional media of JA-stimulated A549 cells. This effect gradually increased with increasing concentrations of either type of Jolkinolide.ConclusionsOur results suggest that JA and JB inhibited VEGF expression in A549 cells through the inhibition of the Akt-STAT3-mTOR signaling pathway, and directly inhibited the proliferation and migration of HUVECs. These findings are of great significance for the development of new plant-derived chemotherapy agents for the treatment of cancer.

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Novel Lycorine Derivatives as Anticancer Agents: Synthesis and In Vitro Biological Evaluation

Cited by 32 publications

References 19 publications

Leveraging botanical resources for crop protection: the isolation, bioactivity and structure–activity relationships of lycoris alkaloids

Leveraging botanical resources for crop protection: the isolation, bioactivity and structure–activity relationships of lycoris alkaloids

A Conserved Inhibitory Mechanism of a Lycorine Derivative against Enterovirus and Hepatitis C Virus

Jolkinolide A and Jolkinolide B Inhibit Proliferation of A549 Cells and Activity of Human Umbilical Vein Endothelial Cells

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