Imperial College London
Alternate

DrNeloferSyed

Faculty of Medicine, Department of Brain Sciences

Senior Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 5292n.syed

 
 
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Location

 

E506Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Tsiailanis:2020:10.1016/j.freeradbiomed.2020.08.007,
author = {Tsiailanis, AD and Renziehausen, A and Kiriakidi, S and Vrettos, EI and Markopoulos, GS and Sayyad, N and Hirmiz, B and Aguilar, M-I and Del, Borgo MP and Kolettas, E and Widdop, RE and Mavromoustakos, T and Crook, T and Syed, N and Tzakos, AG},
doi = {10.1016/j.freeradbiomed.2020.08.007},
journal = {Free Radical Biology and Medicine},
pages = {391--402},
title = {Enhancement of glioblastoma multiforme therapy through a novel Quercetin-Losartan hybrid.},
url = {http://dx.doi.org/10.1016/j.freeradbiomed.2020.08.007},
volume = {160},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Glioblastoma multiforme (GBM) is the most common and aggressive primary malignant brain tumor. Maximal surgical resection followed by radiotherapy and concomitant chemotherapy with temozolomide remains the first-line therapy, prolonging the survival of patients by an average of only 2.5 months. There is therefore an urgent need for novel therapeutic strategies to improve clinical outcomes. Reactive oxygen species (ROS) are an important contributor to GBM development. Here, we describe the rational design and synthesis of a stable hybrid molecule tethering two ROS regulating moieties, with the aim of constructing a chemopreventive and anticancer chemical entity that retains the properties of the parent compounds. We utilized the selective AT1R antagonist losartan, leading to the inhibition of ROS levels, and the antioxidant flavonoid quercetin. In GBM cells, we show that this hybrid retains the binding potential of losartan to the AT1R through competition-binding experiments and simultaneously exhibits ROS inhibition and antioxidant capacity similar to native quercetin. In addition, we demonstrate that the hybrid is able to alter the cell cycle distribution of GBM cells, leading to cell cycle arrest and to the induction of cytotoxic effects. Last, the hybrid significantly and selectively reduces cancer cell proliferation and angiogenesis in primary GBM cultures with respect to the isolated parent components or their simple combination, further emphasizing the potential utility of the current hybridization approach in GBM.
AU  - Tsiailanis,AD
AU  - Renziehausen,A
AU  - Kiriakidi,S
AU  - Vrettos,EI
AU  - Markopoulos,GS
AU  - Sayyad,N
AU  - Hirmiz,B
AU  - Aguilar,M-I
AU  - Del,Borgo MP
AU  - Kolettas,E
AU  - Widdop,RE
AU  - Mavromoustakos,T
AU  - Crook,T
AU  - Syed,N
AU  - Tzakos,AG
DO  - 10.1016/j.freeradbiomed.2020.08.007
EP  - 402
PY  - 2020///
SN  - 0891-5849
SP  - 391
TI  - Enhancement of glioblastoma multiforme therapy through a novel Quercetin-Losartan hybrid.
T2  - Free Radical Biology and Medicine
UR  - http://dx.doi.org/10.1016/j.freeradbiomed.2020.08.007
UR  - https://www.ncbi.nlm.nih.gov/pubmed/32822744
UR  - https://www.sciencedirect.com/science/article/pii/S0891584920312028?via%3Dihub
VL  - 160
ER  -
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