Antiproliferative Activity, Cell Cycle, and Apoptosis Studies of a Series of 6‐Substituted 9H‐Purin‐9‐yl‐pyridinium Derivatives on a Human Cervical Carcinoma Cell Line

Abstract

Better by benzylthio: A series of 6‐substituted 9H‐purin‐9‐yl‐pyridinium derivatives was synthesized and evaluated for their antitumor activity. Compounds included in this study elicit variations in cell‐cycle progression and an increase of apoptotic cells in a caspase‐3‐dependent process.

Recent advances in the design of choline kinase α inhibitors and the molecular basis of their inhibition

“…The cLogP values of these structures are at least twofold higher than the corresponding clogP values of the adenine series, which likely explains the higher antiproliferative effect observed. Treatment of HeLa cells with these compounds caused clear disturbances of cell cycle progression and induction of apoptosis in a caspase‐3‐dependent process 76 . As already mentioned, the presence of a dimethylamino group at position 4 of the pyridinium ring led to a greater effect.…”

“…Treatment of HeLa cells with these compounds caused clear disturbances of cell cycle progression and induction of apoptosis in a caspase-3-dependent process. 74 As already mentioned, the presence of a dimethylamino group at the position 4 of the pyridinium ring led to a greater effect. However, the activity was also favored by short linkers, contrary to that previously observed for adenine counterparts.…”

“…The introduction of a benzylthio substituent at position 6 of the purine heterocyclic ring led to a new series of hChoK inhibitors with an enhanced antiproliferative profile against human cervical carcinoma HeLa cell line. 74 The cLogP values of these structures are at least 2-fold higher than the corresponding clogP values of the adenine series, which likely explains the higher antiproliferative effect observed. Treatment of HeLa cells with these compounds caused clear disturbances of cell cycle progression and induction of apoptosis in a caspase-3-dependent process.…”

“…This first library of nonsymmetric hChoK inhibitors evidenced a modest antiproliferative activity that was associated with their lack of lipophilicity. The introduction of a benzylthio substituent at position 6 of the purine heterocyclic ring led to a new series of hChoK inhibitors with an enhanced antiproliferative profile against human cervical carcinoma HeLa cell line 76 . The cLogP values of these structures are at least twofold higher than the corresponding clogP values of the adenine series, which likely explains the higher antiproliferative effect observed.…”

NMR spectroscopic characterization of new nonsymmetrical bispyridinium choline kinase inhibitors

“…Choline kinase (CK) is the first enzyme for the biosynthesis of phosphatidylcholine, the mayor phospholipid component of mammalian cells and the precursor of second messengers that can activate growth and survival pathways . To target the aberrant choline phospholipid metabolism of cancer cells, we have designed and synthesized nonsymmetrical pyridinium CK inhibitors …”