engleski

Synthesis and anti-proliferative effects of mono- and bis-purinomimetics targeting kinases

A series of mono-pyrrolo[2, 3-d]pyrimidines 4a–4k, unsymmetrical bis-purine isosteres 5a–5e and symmetrical bis-pyrrolo[2, 3-d]pyrimidines 6a and 6b connected via di(1, 2, 3-triazolyl)phenyl linker were synthesized by click chemistry. Whereas mono- 4g and bis-pseudopurine 5e showed selective inhibitory activities on cervical carcinoma (HeLa) cells, bis-pyrrolo[2, 3-d]pyrimidine 6b exhibited potent and selective anti-proliferative effect in the nanomolar range on pancreatic carcinoma (CFPAC-1) cells. Among these, compound 6b induced a significant reduction in the expression level of CDK9 (cyclin-dependent kinase 9)/cyclin T1 in CFPAC-1 cells concomitant with attenuation of proliferative signaling mediated by c-Raf (rapidly accelerated fibrosarcoma) and p38 MAP (mitogen- activated protein) kinases. Our findings encourage further development of novel structurally related analog of 6b to obtain more selective anticancer agent for treating pancreatic canc

pyrrolo[2, 3-d]pyrimidines ; purinomimetics ; 1, 2, 3-triazole ; anticancer ; pancreatic carcinoma (CFPAC-1)

nije evidentirano