alexa A G-quadruplex/i-motif Switch In The HRAS Promoter As Target For Anthrathiophenediones That Show A Strong Anti-proliferative Activity In Urinary Bladder Cancer Cells
ISSN: 2161-0444

Medicinal Chemistry
Open Access

Like us on:
OMICS International organises 3000+ Global Conferenceseries Events every year across USA, Europe & Asia with support from 1000 more scientific Societies and Publishes 700+ Open Access Journals which contains over 50000 eminent personalities, reputed scientists as editorial board members.

Open Access Journals gaining more Readers and Citations

700 Journals and 15,000,000 Readers Each Journal is getting 25,000+ Readers

This Readership is 10 times more when compared to other Subscription Journals (Source: Google Analytics)

Share This Page

Additional Info

Loading
Loading Please wait..
 

3rd International Conference on Medicinal Chemistry & Computer Aided Drug Designing
December 08-10, 2014 DoubleTree by Hilton Hotel San Francisco Airport, USA

Luigi E Xodo, Susanna Cogoi and Andrey Shchekotikhin
ScientificTracks Abstracts: Med Chem
DOI: 10.4172/2161-0444.S1.011
Abstract
Evidence that guanine repeats of genomic DNA are able to adopt non-canonical G-quadruplex structures is rapidly growing, in particular since it was demonstrated that these unusual DNA structures occur in the cell. Recently, we have discovered that a G-quadruplex/I-motif switch in the HRAS promoter controls gene expression (a) and we thus designed small molecules that efficiently target the molecular switch. These quadruplex-binding ligands will open up a new approach in cancer therapy (a). In the present work we tested a number of antrathiophenediones with two alkyl side arms each bearing a terminal methylamino (2) or delocalized cationic guanidino (1) or chloroacetamidino (3-7) group. We discovered that the chloroacetamidines penetrate cancer cells more efficiently than non-cancer cells, and that they locate in the cytoplasm and nucleus. Among the analogs tested, compound 3, with two ethyl side chains, was found particularly bioactive in urinary bladder cancer cells, as it extinct the expression of oncogenic HRAS. We found that 3 stabilizes the G-quadruplex/I-motif switch and inhibits MAZ, a transcription factor that unfolds the switch and activates transcription. The extinction of HRAS results in the blockade of the cell cycle in the G2/M phase and in suppression of cyclin D1. This brings the cells to apoptosis (PARP-1 cleavage, caspases 3/9 activation). The impact of compound 3 on pathways downstream of RAS was also analyzed.
Biography
Luigi E Xodo had his degree in chemistry at the University of Trieste (Italy). He worked for a couple of years at the Universities of Reading and Surrey (UK) before being appointed Associate Professor at the University of Trieste. At present, he is full Professor of Biochemistry at the University of Udine (Italy). He published more than 90 papers in reputed journals.
image PDF   |   image HTML
 
Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

[email protected]

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

[email protected]

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords