Modeling Study On Pharmacophore Conformation Of Caffeic Acid Derivatives And Platensimycin

With the development of computational chemistry, the molecular designingtechnologies are to be the powerful tools for new medicals. This paper presents thechemical calculation of caffeic acid derivatives and docking of latensimycin/platencin,and discusses the relationship between the structure and activity.The caffeic acid derivatives, water-soluble components of Danshen, havepowerful anti-oxidation activity and used to treat the cardiovascular diseases in theclinic. Using density function theory, choosing b3lyp/6-31g*, we analyzed single pointenergy, dipole moment, nuclear repulsion energy and HOMO/LUMO. Comparingwith thier bioactivities, the relationship between structure and antioxidant activity weranalyzed. The results showed that the more–OH group substitute on benzene, thestronger the antioxidant activity. The catechol has the stronger antioxidant activity,and any position is replaced by–OH can contribute the antioxidant activity.Platencin and platensimycin are the newest inhibitors of FabF. We used FlexX toanalyze the modeling docking of Platencin/platensimycin and FabF. CScore data wereapplied to help selecet the final and the reasonable pharmacophoric conformationmodel. The top of benzene ring of Platencin and platensimycin had dock with theFabF(C163Q, H303, H340, F400), and the tail side-chain was out of the activitypocket. Between the receptor FabF and inhibitors, strong hydrophilicity and weakelectrostatic interaction were observed, not hydrogen bond. Compared withplatensimycin with higher clozing pocket activity, platencin was closer to the pocketwith higher binding activity and substrate competition. The design of the FabFinhibitors could be concerned by two ways. One is improving the hydrophilicity onthe top side, the other is increasing the steric hindrance on the tail side to get newantibiotics.