Search

Using the aminopyrazole scaffold, N-[5-(4-bromophenyl)-1H-pyrazol-3-yl]carbamothioyl]benzamide was synthesized as a new anti-proliferative agent, hypothesized to target as a specific molecular substrate, several protein kinases. This compound (PRZ) showed antiproliferative and cytotoxic effects in various human cancer cell lines. We assessed the effect of PRZ, along with the effects of cisplatin (CPT), methotrexate (MTX) and of their binary combinations with PRZ on Triticum aestivum root elongation test. We assessed phenomena such as antagonism or synergism, for a better understanding of the mechanisms underlying the anti-proliferative effect of PRZ. MTX and, in a lesser extent, PRZ inhibited cell growth and differentiation. More significant, their equimolar mixture had a more intense effect than MTX alone, but lower than the sum of the effects of each individual compound. The partially additive effect suggests a related mechanism of action for the two compounds. No significant effect was noticed for cisplatin alone, nor for its association with PRZ. [ABSTRACT FROM AUTHOR]

The use of cheminformatics in the process of choosing the appropriate leads is becoming essential in the academic environment. The role of Aurora-A kinase as a major regulator of the cellular processes and the potential of its inhibitors in the treatment of cancer renders their research a top priority in the oncology studies. In this paper, we performed a structural profiling of the Aurora-A inhibitors in the search for new leading structures in the development of future Aurora-A kinase inhibitors. Based on the statistical analyses performed, the important descriptors for the Aurora-A affinity were identified and a set of rules of thumbs were elaborated in order to screen structural databases for new Aurora-A inhibitors. Thus, the hydrogen bonding capacity and the presence of nitrogen atoms in pyrazole, pyrimidine, piperazine or piperidine scaffold are prerequisite keys in order to increase the target affinity of Aurora-A inhibitors. [ABSTRACT FROM AUTHOR]