ABSTRACT
Three synthesized series of compounds based on a thiazolidine core allowed identification of potent inhibitors of thymidylate synthase X. The evaluation of the catalytic activity of the enzyme in the presence of these molecules revealed two distinct classes of compounds that inhibit ThyX with submicromolar concentrations, which could lead, after optimization, to effective inhibitors with potential biomedical interest.
Subject(s)
Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Thiazolidines/chemical synthesis , Thiazolidines/pharmacology , Thymidylate Synthase/antagonists & inhibitors , Drug Design , Drug Evaluation, Preclinical , Enzyme Inhibitors/chemistry , Molecular Conformation , Stereoisomerism , Structure-Activity Relationship , Thiazolidines/chemistry , Thymidylate Synthase/chemistry , Time FactorsABSTRACT
The preparation of a new family of lipothiourea is reported using an automatic synthetic workstation. In these compounds the headgroups were made from single thiourea derivatives. The physicochemical properties and the transfection efficiency of several members of the family were studied. It was found that in the presence of DMPC small lipoplexes could be prepared. In opposite to the previously described di- and tri-lipothioureas most of these liposomes are unstable overtime. In addition, even the stable ones show no transfecting efficiency. All these data demonstrate that at least two thiourea groups are necessary to produce stable lipoplexes, to condense DNA and to give efficient transfection.
