International cooperation in the development of anticancer agents based on naphthoquinone compounds

Programme

Projects for capacity building for participation in the horizon europe programme for the year 2025

Strategic priority

I. Health

Strategic direction

Pharmaceutical preparations from local raw materials

Code
25.80015.8007.04POE
Duration
2025
Laboratories/Centers
Project manager
Abstract

This project aims to facilitate the exchange of knowledge and expertise in the field of research (organic synthesis and quantum-chemical calculations) and project management by organizing mobility internships between the involved partners. Through these exchanges, the goal is to strengthen individual competencies, develop strategic collaborations, and promote integration into European research networks.

Results, activities

Within the framework of this project, complex investigations were carried out aimed at the synthesis, study, and evaluation of naphthoquinonic compounds and their derivatives. The goal was to identify structures with high antitumor potential and to elucidate the structure–activity relationship (SAR). The synthesis activities included the development and optimization of efficient procedures for functionalizing juglone, 2-hydroxyjuglones, and other quinone cores, as well as the creation of an extensive library of hybrid derivatives through reductive alkylation, stereoselective cyclizations, reactions with aliphatic and aromatic amines, and coupling with bioactive fragments. Monocyclic, polycyclic, and complex tetracyclic systems were obtained, and the structures of several compounds were confirmed via single-crystal X-ray diffraction. The synthesized compounds were tested for bioactivity at the Rega Institute, KU Leuven (Belgium), across eight cancer cell lines and on peripheral blood mononuclear cells (PBMC).
The results demonstrated moderate to very good cytotoxic activity, with increased selectivity observed for derivatives substituted at the C3 position of the naphthoquinone ring. The most promising substances were investigated in detail regarding their structure–activity dependence, providing the foundation for the subsequent synthesis of targeted derivatives. To understand the compounds' mechanisms of action, the structural and bioactivity data were shared with partners at the "Carol Davila" University of Medicine and Pharmacy, who are conducting computational docking and molecular modeling studies. This approach allows for the elucidation of interaction mechanisms with cancer cells and provides directions for structural optimization.
The project has strengthened national and international collaborations, enabled the experimental and computational testing of synthesized molecules, and contributed to the development of an integrated base for drafting international research and innovation grant proposals. Currently, suitable calls are being identified to submit a project proposal on the described topic. Furthermore, together with a local consortium, the "INSPIRE" project (ID 101305163) was submitted under the topic HORIZON-MSCA-2025-CITIZENS-01-01 (European Researchers' Night and Researchers at Schools 2026-2027), with Moldova State University (USM) serving as the consortium leader.