Molecular Modeling studies based on molecular mechanics and semi-empirical methods have been carried out for PGT and its metabolites in order to gain insight into excretion, reactivity and toxic effects of PGT. All metabolites are kinetically labile as indicated by LUMO-HOMO energy difference. The molecular modeling analysis shows that M2 metabolite is readily excreted in urine as its calculated solvation energy is highest. Further, it is found that M1 metabolite might be responsible for edema as it contains acidic group which can form salt bridge with Arg 120 of COX-1. All the metabolites are more reactive than PGT towards nucleophilic attack as indicated by lowest electron affinity of PGT. M3 has the highest HOMO (lowest ionization potential) energy so it will be most susceptible towards electrophilic attack.
Loading....