Collection of alkenylcoumarin derivatives as Taq DNA polymerase inhibitors: SAR and in silico simulations

GARRO, HUGO A.; PUNGITORE, CARLOS R.; BRUNA-HAUPT, EZEQUIEL; GUTIÉRREZ, LUCAS

MEDICINAL CHEMISTRY RESEARCH

BIRKHAUSER BOSTON INC

Año: 2018 vol. 27 p. 1432 - 1442

1054-2523

Using a feasible method, we generated a small focused library of structurally related alkenylcoumarins. These compounds were evaluated as potential antitumoral agents against Taq DNA polymerase. 6-(pent-4-enyloxy)-coumarin (7) IC50 = 48.33 ± 2.85 μM was defined as a small molecule able to disturb DNA replication. Docking and Molecular Dynamic Simulations suggest an active-site binding. Structure/activity relationship was reasonably established. Compound 7 represents a potential structure for further studies in the development of new anti-cancer DNA/polymerase binding agents.