Small molecule purine and pseudopurine derivatives: synthesis, cytostatic evaluations and investigation of growth inhibitory effect in non-small cell lung cancer A549.

摘要: Novel halogenated purines and pseudopurines with diverse aryl-substituted 1,2,3-triazoles were prepared. While p-(trifluoromethyl)-substituted 1,2,3-triazole in N-9 alkylated purine 3-deazapurine was critical for strong albeit unselective activity on pancreatic adenocarcinoma cells CFPAC-1,1-(p-fluorophenyl)-1,2,3-triazole derivative of 7-deazapurine showed selective cytostatic effect metastatic colon cancer SW620. Importantly, 1-(p-chlorophenyl)-1,2,3-triazole-tagged benzimidazole displayed the most pronounced highly inhibitory nM range non-small cell lung A549. This compound revealed to target molecular processes at extracellular side inside plasma membrane regulated by GPLD1 growth factor receptors PDGFR IGF-1R leading inhibition proliferation induction apoptosis mediated p38 MAP kinase NF-κB, respectively. Further optimisation this as reduce its toxicity normal may lead development novel agent effective against cancer.