Synthesis and migrastatic activity of cytochalasin analogues lacking a macrocyclic moiety

0581608 - ÚOCHB 2025 RIV GB eng J - Journal Article
Formánek, B. - Dupommier, D. - Volfová, T. - Rimpelová, S. - Škarková, A. - Herciková, J. - Rösel, D. - Brábek, J. - Perlíková, Pavla
Synthesis and migrastatic activity of cytochalasin analogues lacking a macrocyclic moiety.
RSC MEDICINAL CHEMISTRY. Roč. 15, č. 1 (2024), s. 322-343. E-ISSN 2632-8682
R&D Projects: GA MŠMT LX22NPO5102
Institutional support: RVO:61388963
Keywords : actin polymerization * cellular structures * alkyl-halides
Impact factor: 4.1, year: 2022
Method of publishing: Open access
https://doi.org/10.1039/D3MD00535F

Cytochalasans are known as inhibitors of actin polymerization and for their cytotoxic and migrastatic activity. In this study, we synthesized a series of cytochalasin derivatives that lack a macrocyclic moiety, a structural element traditionally considered essential for their biological activity. We focused on substituting the macrocycle with simple aryl-containing sidechains, and we have also synthesized compounds with different substitution patterns on the cytochalasin core. The cytochalasin analogues were screened for their migrastatic and cytotoxic activity. Compound 24 which shares the substitution pattern with natural cytochalasins B and D exhibited not only significant in vitro migrastatic activity towards BLM cells but also demonstrated inhibition of actin polymerization, with no cytotoxic effect observed at 50 mu M concentration. Our results demonstrate that even compounds lacking the macrocyclic moiety can exhibit biological activities, albeit less pronounced than those of natural cytochalasins. However, our findings emphasize the pivotal role of substituting the core structure in switching between migrastatic activity and cytotoxicity. These findings hold significant promise for further development of easily accessible cytochalasan analogues as novel migrastatic agents.
Permanent Link: https://hdl.handle.net/11104/0349710