Novel Substituted Purine Isosteres: Synthesis, Structure-Activity Relationships and Cytotoxic Activity Evaluation.
Spyridon DimitrakisEfthymios-Spyridon GavriilAthanasios PousiasNikolaos LougiakisPanagiotis MarakosNicole PouliKaterina GiotiRoxane TentaPublished in: Molecules (Basel, Switzerland) (2021)
A number of pyrrolo[2,3- c ]pyridines, pyrrolo[3,2- d ]pyrimidines and pyrazolo[4,3- d ]pyrimidines were designed and synthesized as antiproliferative agents. The target compounds possessed selected substituents in analogous positions on the central scaffold that allowed the extraction of interesting SARs. The cytotoxic activity of the new derivatives was evaluated against prostatic (PC-3) and colon (HCT116) cell lines, and the most potent analogues showed IC 50 values in the nM to low µM range, while they were found to be non-toxic against normal human fibroblasts (WI-38). Flow cytometric analysis of DNA content revealed that the most promising derivative 14b caused a statistically significant accumulation of PC-3 cells at G 2 /M phase and induced apoptosis in PC-3 cells.
Keyphrases
- induced apoptosis
- endoplasmic reticulum stress
- molecular docking
- oxidative stress
- endothelial cells
- signaling pathway
- photodynamic therapy
- circulating tumor
- cell free
- single molecule
- structure activity relationship
- induced pluripotent stem cells
- radical prostatectomy
- anti inflammatory
- pluripotent stem cells
- cell proliferation
- water soluble
- oxide nanoparticles