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Updated: Jun 26, 2025

Microwave-Assisted Preparation of 1-Aryl-1H-pyrazole-5-amines
Published on: June 23, 2019
Design, Synthesis, Antitumor Activity and NMR-Based Metabolomics of Novel Amino Substituted Tetracyclic
Nataša Perin1, Borka Lončar2, Matej Kadić1
1Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 19, HR-10000, Zagreb, Croatia.
Abstract:
Newly prepared tetracyclic imidazo[4,5-b]pyridine derivatives were synthesized to study their antiproliferative activity against human cancer cells. Additionally, the structure-activity was studied to confirm the impact of the N atom position in pyridine nuclei as well as the chosen amino side chains on antiproliferative activity. Targeted amino substituted regioisomers were prepared by using uncatalyzed amination from corresponding chloro substituted precursors. The most active compounds 6 a, 8 and 10 showed improved activity in comparison to standard drug etoposide with IC50 values in a nanomolar range of concentration (0.2-0.9 μM). NMR-based metabolomics is a powerful instrument to elucidate activity mechanism of new chemotherapeutics. Multivariate and univariate statistical analysis of metabolic profiles of non-small cell lung cancer cells before and after exposure to 6 a revealed significant changes in metabolism of essential amino acids, glycerophospholipids and oxidative defense. Insight into the changes of metabolic pathways that are heavily involved in cell proliferation and survival provide valuable guidelines for more detailed analysis of activity metabolism and possible targets of this class of bioactive compounds.
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