Validation of NBD-coupled taurocholic acid for intravital analysis of bile acid transport in liver and kidney of mice.

Fluorophore-coupled bile acids (BA) represent an important tool for intravital analysis of BA flux in animal models of cholestatic diseases. However, addition of a fluorophore to a BA may alter transport properties. We developed and validated a 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole-coupled taurocholic acid (3β-NBD-TCA) as a probe for intravital analysis of BA homeostasis.

Synthesis and Antiproliferative Activity of Cisplatin-3-Chloropiperidine Conjugates.

We report the synthesis and characterization of two novel cisplatin- alkylating agents conjugates. Combining a platinum based cytostatic agent with a sterically demanding alkylating agent could potentially induce further DNA damage, block cell repair mechanisms and keep the substrate active against resistant tumor cell lines. The 3-chloropiperidines utilized as ligands in this work are cyclic representatives of the N-mustard family and were not able to coordinate platinum on their own.

Secondary 3-Chloropiperidines: Powerful Alkylating Agents.

In previous works, we demonstrated that tertiary 3-chloropiperidines are potent chemotherapeutics, alkylating the DNA through the formation of bicyclic aziridinium ions. Herein, we report the synthesis of novel secondary 3-chloropiperidine analogues. The synthesis incorporates a new procedure to monochlorinate unsaturated primary amines utilizing N-chlorosuccinimide, while carefully monitoring the temperature to prevent dichlorination.