Collection of alkenylcoumarin derivatives as Taq DNA polymerase inhibitors: SAR and in silico simulations
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.
KeywordsDNA polymerase Antitumoral SAR Coumarin Natural Products
This research was supported by CONICET (PIP 00360) and UNSL (PROICO 02/2516). EFB thank CONICET for doctoral fellowship. HAG thank for post-doctoral position in the Max Planck Laboratory for Structural Biology, Chemistry, and Molecular Biophysics of Rosario (MPLbioR). We wish to thank to Lic. M. Ferrari, Dr. C. Ardanáz, and Dr. G. Labadie for their help. Also, we wish to thank to Dra. C. García and Prof. V. Martín from IUBO (Spain) for their help in the use of HRMS. We wish specially thank to Drs. L. Mascotti and M. Juri-Ayub for DNA material gently provided. We appreciate revision of the manuscript by staff from the “Instituto de Lenguas, Universidad Nacional de San Luis”. This work is a part of the doctoral thesis of EFB.
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Conflict of interest
The authors declare that they have no conflict of interest.
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