Chromone-based A3 receptor ligands: a new challenge in drug development for anticancer therapy

• Type: Summary of Presentation in a National Conference
• Date: 2010

Authors

Alexandra Gaspar (Author) FCUP; Nuno Milhazes (Author) Other; Jorge Garrido (Author) Other; Eugenio Uriarte (Author) Other; Sonja Kachler (Author) Other; Karl Norbert Klotz (Author) Other; Fernanda Borges (Author) FCUP

Conference proceedings National

Title: XVII Congresso Nacional de Bioquímica

Pages: 347-347

XVII Congresso Nacional de Biquímica

Porto, Portugal, 15 – 17 December 2010

Scientific classification

FOS: Engineering and technology > Chemical engineering

CORDIS: Physical sciences > Chemistry > Analytical chemistry > Clinical chemistry ; Physical sciences > Chemistry > Biochemistry

Other information

Abstract (EN): Cancer is a very complex disease, linked with different initiating causes, cofactors and promoters, and several types of cellular damage. Advancing knowledge on the cellular and molecular biology of the processes that regulate cell proliferation, cell differentiation and cellular responses to external signals make a number of potential targets available for new approaches to treat cancer. This has provided a wealth of information about the biochemistry and biology of the cancer cell and how it differs from a normal one. Accordingly, these are the differences that must be exploited in the development of the next generation of anticancer agents. During the last decade different approaches to treating cancer have been developed based mainly on specific targets that are mostly expressed in tumor but not in normal cells. Furthermore, it is now recognized that individualizing therapy for patients being treated with anticancer agents is an important goal, leading to the prediction of agents that will be efficient. Interestingly, adenosine receptor (AR) levels in various tumor cells are upregulated, a finding which may suggest that a specific AR may serve as a biological marker and as a target for specific ligands leading to cell growth inhibition. These facts prompted to the development of novel, selective and potent AR receptor ligands suitable for chemotherapeutic purposes. Lead discovery and optimization, guided by structure-activityrelationships (SAR) and quantitative-structure-activity relationships (QSAR) of new AR ligands based on chromone scaffold is the aim of the present work. Accordingly, a library of novel chromone derivatives was obtained through the application of innovative parallel and solid phase synthetic strategies (PCT/IB2008/050674). The compounds have been screened for their affinity towards different ARs subtypes (A1, A2A, A2B and A3) by radioligand binding assays, namely evaluating their ability to displace [3H]-DPCPX, [3H]- ZM241385, [3H]-DPCPX, and [3H]-NECA from cloned human A1, A2A, A2B, and A3 adenosine receptors. The results obtained so far will be presented in this communication.

Language: Portuguese

Type (Professor's evaluation): Scientific