Research

Photochemistry toolbox for discovery of advanced ATP-competitive chemical probes with Topoisomerase IIalpha inhibitory activity

Code:

N1-0172

Range:

01. January 2021 - 31. December 2023

Range:

0,51 FTE

Leader:

Janez Ilaš

Field:

1-09 Natural sciences and Mathematics - Pharmacy

Abstract:

Due to an ageing population, the challenges associated with cancer treatment are growing. The use of conventional chemotherapeutic agents is often limited because of their side effects. Moreover, resistance of cancer cells to chemotherapeutic drugs often results in failure of treatment. The project aims to contribute to the discovery and development of new anticancer agents with improved properties by providing novel topoisomerase II inhibitors.
Topoisomerase II is an enzyme involved in cell replication, whose inhibition leads to cell death. Several topoisomerase II inhibitors are already in clinics, however because of their serious side effects, inhibitors with improved safety would be needed.
We would develop synthetic routes for their preparation and study their efficiency in subsequent biological studies. As a step further towards safer therapies, we plan to combine our work with cutting-edge approaches of the so-called photopharmacology. Via appropriate chemical modifications we plan to render our enzyme inhibitors photoresponsive, whose activity could be turned on or off even in tissues in a controlled manner by light.
Applying approaches of different fields in an integrated manner, our project might lead to: i) a better understanding of the functioning and efficiency of a novel class of ATP-competitive topoisomerase II inhibitors, ii) to new chemical entities with improved anticancer properties for drug development, iii) important proof-of-concept results on the applicability of photopharmaceuticals in cancer treatment.