RESUMEN
Inhibition of mushroom tyrosinase was observed with synthetic dihydropyrano[3,2-b]chromenediones. Among them, DHPC04 displayed the most potent tyrosinase inhibitory activity with a Ki value of 4 µm, comparable to the reference standard inhibitor kojic acid. A kinetic study suggested that these synthetic heterocyclic compounds behave as competitive inhibitors for the L-DOPA binding site of the enzyme. Furthermore, molecular modeling provided important insight into the mechanism of binding interactions with the tyrosinase copper active site.
Asunto(s)
Agaricales/enzimología , Benzopiranos/química , Benzopiranos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Monofenol Monooxigenasa/antagonistas & inhibidores , Agaricales/efectos de los fármacos , Benzopiranos/síntesis química , Inhibidores Enzimáticos/síntesis química , Cinética , Modelos Moleculares , Monofenol Monooxigenasa/metabolismo , Pironas/farmacología , Relación Estructura-ActividadRESUMEN
Tubulin is a potent molecular target for development of anticancer agents. In this report, the binding of non-steroidal anti-inflammatory drugs as tubulin inhibitors potential are investigated by extensive computational techniques, such as, molecular docking, molecular dynamics simulations and binding free energy calculations. The results suggest that a potent indomethacin derivative inhibits the tubulin polymerization by interacting on the colchicine-site binding. This potential chemotherapeutic agent showed high stability in the molecular dynamics simulations, when complexed on the same binding site of colchicine, a potent and toxic, tubulin inhibitor. Then, our results can be useful designing new compounds for cancer treatments.
