Dimeric 1,3-Phenylene-bis(piperazinyl benzimidazole)s: Synthesis and Structure鈥揂ctivity Investigations on their Binding with Human Telomeric G-Quadruplex DNA and Telomerase Inhibition Properties

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• 作者：Akash K Jain ; Ananya Paul ; Basudeb Maji ; K. Muniyappa ; Santanu Bhattacharya
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：April 12, 2012
• 年：2012
• 卷：55
• 期：7
• 页码：2981-2993
• 全文大小：641K
• 年卷期：v.55,no.7(April 12, 2012)
• ISSN：1520-4804

文摘

Ligand-induced stabilization of G-quadruplex structures formed by the human telomeric DNA is an active area of research. The compounds which stabilize the G-quadruplexes often lead to telomerase inhibition. Herein we present the results of interaction of new monomeric and dimeric ligands having 1,3-phenylene-bis(piperazinyl benzimidazole) unit with G-quadruplex DNA (G4DNA) formed by human telomeric repeat d[(G₃T₂A)₃G₃]. These ligands efficiently stabilize the preformed G4DNA in the presence of 100 mM monovalent alkali metal ions. Also, the G4DNA formed in the presence of low concentrations of ligands in 100 mM K⁺ adopts a highly stable parallel-stranded conformation. The G-quadruplexes formed in the presence of the dimeric compound are more stable than that induced by the corresponding monomeric counterpart. The dimeric ligands having oligo-oxyethylene spacers provide much higher stability to the preformed G4DNA and also exert significantly higher telomerase inhibition activity. Computational aspects have also been discussed.