Technological Advances in Preclinical Drug Evaluation: The Role of -Omics Methods.

Preclinical drug development is an essential step in the drug development process where the evaluation of new chemical entities occurs. In particular, preclinical drug development phases include deep analysis of drug candidates' interactions with biomolecules/targets, their safety, toxicity, pharmacokinetics, metabolism by use of assays in vitro and in vivo animal assays. Legal aspects of the required procedures are well-established. Herein, we present a comprehensive summary of current state-of-the art approaches and techniques used in preclinical studies. In particular, we will review the potential of new, -omics methods and platforms for mechanistic evaluation of drug candidates and speed-up of the preclinical evaluation steps.

Synthesis and in vitro antiproliferative evaluation of novel N-alkylated 6-isobutyl- and propyl pyrimidine derivatives.

A series of novel N-alkylated C-6-isobutyl- or -propyl pyrimidine derivatives were synthesized and their antiproliferative effect was evaluated on a panel of tumor cell lines including leukemia cell line K562 and normal diploid human fibroblasts. N-methoxymethylated 5-methylpyrimidin-2,4-dione with di(benzyloxy)isobutyl at C-6 (14b) showed the strongest effect on the cell growth at micromolar concentrations. Mechanisms of action for the lipophilic compound 14b predicted in silico, pointed to its anticancer and antimetastatic potential exerted through inhibition of DNA or RNA polymerases and adhesion molecules. The latter mechanism has been supported in vitro for adherent tumor cell lines.