Molecular Modelling Analysis of the Metabolism of Ambroxol

摘要

Ambroxol (AMB) is used to treat acute and chronic bronchitis, bronchiectasia and lung tuberculosis and possesses antioxidant properties. Molecular modelling analyses based on molecular mechanics, semi-empirical (PM3) and DFT (at B3LYP/6-31G* level) calculations show that AMB and its metabolites DHTQ and DBABA have LUMO-HOMO energy differences of 5.11, 5.01 and 4.28 eV, respectively from DFT calculations. The values indicate that AMB and DHTQ would be significantly more inert kinetically than DBABA. The molecular surfaces of AMB, DHTQ and DBABA are found to abound in neutral green regions so that the compounds can undergo lyophilic attack. The molecular surfaces of the three compounds are also found to possess significant amounts of electron-rich (red and yellow) regions so that they may be subject to electrophilic attacks as well. However, the compounds may not undergo significant nucleophilic attacks as their molecular surfaces do not abound in electron-deficient regions. The presence of neutral and electron-rich regions may impart antioxidant properties to AMB and its metabolites.