scholarly journals Phthalimide Derivative Shows Anti-angiogenic Activity in a 3D Microfluidic Model and No Teratogenicity in Zebrafish Embryos

2019 ◽  
Vol 10 ◽  
Author(s):  
Annalisa Mercurio ◽  
Lucy Sharples ◽  
Filomena Corbo ◽  
Carlo Franchini ◽  
Angelo Vacca ◽  
...  
Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1318 ◽  
Author(s):  
Ali S. Alqahtani ◽  
Fahd A. Nasr ◽  
Omar M. Noman ◽  
Muhammad Farooq ◽  
Tariq Alhawassi ◽  
...  

Commiphora myrrh resin (Myrrh) has been used in traditional Arabic medicine to treat various inflammatory diseases. Two furano-sesquiterpenoids, 2-methoxyfuranodiene (CM1) and 2-acetoxyfuranodiene (CM2), were isolated from the chloroform fraction of the ethanolic extract of Arabic Commiphora myrrh resin. The cytotoxicity of the compounds was evaluated using human liver carcinoma, breast cancer cells (HepG2 and MCF-7, respectively) and normal human umbilical vein endothelial cells (HUVECs) cell lines. The development toxicity and anti-angiogenic activity of both compounds were also evaluated using zebrafish embryos. Cell survival assays demonstrated that both compounds were highly cytotoxic in HepG2 and MCF7 cells, with IC50 values of 3.6 and 4.4 µM, respectively. Both compounds induced apoptosis and caused cell cycle arrest in treated HepG2 cells, which was observed using flow cytometric analysis. The development toxicity in zebrafish embryos showed the chronic toxicity of both compounds. The toxicity was only seen when the embryos remained exposed to the compounds for more than three days. The compound CM2 showed a significant level of anti-angiogenic activity in transgenic zebrafish embryos at sublethal doses. Thus, we demonstrated the cytotoxic properties of both compounds, suggesting that the molecular mechanism of these compounds should be further assessed.


2016 ◽  
Vol 11 (4) ◽  
pp. 1934578X1601100 ◽  
Author(s):  
Weihuan Huang ◽  
Xiaobin Yu ◽  
Ning Liang ◽  
Wei Ge ◽  
Hin Fai Kwok ◽  
...  

Centipeda minima is a Chinese herbal medicine used in the treatment of various diseases including cancer. An ethanol extract of the herb, its four fractions with different polarities, and two volatile oils prepared by steam distillation (SD) and supercritical fluid extraction (SFE) were investigated for their anti-angiogenic activity in a wild-type zebrafish model using a quantitative endogenous alkaline phosphatase (EAP) assay. The SFE oil displayed potent anti-angiogenic activity. Fifteen sesquiterpene lactones (SLs; compounds 1–15) isolated from the SFE oil were evaluated for their anti-angiogenic effect. Results revealed that pseudoguaianolide type SLs (1–8) inhibited vessel formation in the zebrafish embryos while guaianolide type SLs (9–15) showed little effect. Among the active ones, 6- O-angeloylenolin (1), a major component of SFE oil, possessed the strongest effect by reducing vessel formation in zebrafish embryos to 40% of the control value at 29.7 μM. Further study using the Tg ( fli1a:EGFP) y1-type zebrafish model revealed that it blocked both intersegmental blood vessels (ISVs) and subintestinal vessels plexus (SIVs) formation in zebrafish embryos. Real-time polymerase chain reaction assay on the wild-type zebrafish embryos suggested that 6- O-angeloylenolin affected multiple molecular targets related to angiogenesis including VEGF receptor, angiopoietin, and its receptors. Taken together, our findings demonstrate that C. minima possesses anti-angiogenic activity, and 6- O-angeloylenolin is a promising candidate for the development of an anti-angiogenic agent.


2012 ◽  
Vol 27 (9) ◽  
pp. 1368-1375 ◽  
Author(s):  
Xiaobin Yu ◽  
Yao Tong ◽  
Xiao-Qiang Han ◽  
Hin-Fai Kwok ◽  
Grace Gar-Lee Yue ◽  
...  

2017 ◽  
Vol 12 (7) ◽  
pp. 497-499
Author(s):  
Kalimuthu Kalishwaralal ◽  
Subhaschandrabose Jeyabharathi ◽  
Krishnan Sundar ◽  
Azhaguchamy Muthukumaran

Author(s):  
Joachim Delasoie ◽  
Aleksandar Pavic ◽  
Noémie Voutier ◽  
Sandra Vojnovic ◽  
Aurélien Crochet ◽  
...  

Synthesized and characterized a series of rhenium(I) trycarbonyl-based complexes with increased lipophilicity. Two of these novel compounds were discovered to possess remarkable anticancer, anti-angiogenic and antimetastatic activity <i>in vivo</i> (zebrafish-human CRC xenograft model), being effective at very low doses (1-3 µM). At doses as high as 250 µM the complexes did not provoke toxicity issues encountered in clinical anticancer drugs (cardio-, hepato-, and myelotoxicity). The two compounds exceed the antiproliferative and anti-angiogenic potency of clinical drugs cisplatin and sunitinib-malate, and display a large therapeutic window.


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