OPENSCREEN

The Subproject “Organization and Operation of the Research Infrastructure OPENSCREEN-GR/NHRF” concerns the establishment of a research infrastructure at the Institute of Biology, Medicinal Chemistry, and Biotechnology of the National Hellenic Research Foundation (NHRF), within the framework of the “OPENSCREEN-GR” project. Its aim is the optimization of hit compounds, which have been characterized through the activities of the other research infrastructures within OPENSCREEN-GR. Efforts will be made to maintain and expand the infrastructure by attracting users beyond the current partners of OPENSCREEN-GR.

In the context of drug discovery and development, an important stage is the optimization of initially characterized bioactive compounds for a specific target. These compounds often lack either the required activity or the structural features needed to be suitable for further development as potential drugs. Therefore, the synthesis of optimized analogues through synthetic modifications of the original structures is necessary. This approach generates small focused libraries of compounds to derive structure-activity relationships (SARs).

The process is iterative, allowing only compounds with the desired biological profile to be selected for preclinical testing, resulting in significant resource savings. Modifications of the hit structures will be guided by in silico interaction with the biological target, as well as by ADME-Tox property predictions using the QiKProp program. This strategy enables structural modifications aimed at increasing activity while avoiding adverse effects on physicochemical properties such as solubility, protein binding, membrane permeability, and lipophilicity. Additionally, the bioisosteric replacement strategy will be applied during the hit-to-lead (H2L) optimization process.

Modern organic synthesis methods, including high-energy techniques (microwave, ultrasound) and parallel synthesis, will be employed to generate the new analogues. The resulting compounds will be isolated in pure form using chromatography techniques and characterized by one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy, and high-resolution mass spectrometry (HR-MS).