Novel Oligopyrrole Carboxamide based Nickel(II) and Palladium(II) Salens, Their Targeting of Human G-Quadruplex DNA, and Selective Cancer Cell Toxicity

Ali, Asfa and Kamra, Mohini and Roy, Soma and Muniyappa, K and Bhattacharya, Santanu (2016) Novel Oligopyrrole Carboxamide based Nickel(II) and Palladium(II) Salens, Their Targeting of Human G-Quadruplex DNA, and Selective Cancer Cell Toxicity. In: CHEMISTRY-AN ASIAN JOURNAL, 11 (18). pp. 2542-2554.

PDF Che_11-18_2542_2016.pdf - Published Version Restricted to Registered users only Download (1MB) | Request a copy

Abstract

DNA targeting by various metal complexes is a key strategy toward the restriction of cancer cell proliferation. Toward this end, we designed and synthesized novel salen-based Ni-II and Pd-II metal complexes with positively charged flanking side chains comprising N-methylpyrrole carboxamides of varying lengths. The compounds showed high specificity toward G-quadruplex DNA over duplex DNA. Sufficient inhibition of the telomerase activity was observed, which was ascertained by the prominent restriction of cancer cell proliferation in the long-term cell viability and telomerase inhibition assays. The compounds exhibited selective cancer cell death following an apoptotic pathway. Analysis of the binding mode showed partial stacking of the salen moiety over the G-tetrads and association of the pendant oligopyrrole carboxamide units with the grooves. The conjugation of the tetrad-binding metal salen core with groove-oriented flexible oligopyrrole moieties resulted in the high selectivity and stabilization of the human G-quadruplex DNA structures.

Item Type:	Journal Article
Publication:	CHEMISTRY-AN ASIAN JOURNAL
Additional Information:	Copy right for this article belongs to the WILEY-V C H VERLAG GMBH, POSTFACH 101161, 69451 WEINHEIM, GERMANY
Department/Centre:	Division of Biological Sciences > Biochemistry Division of Chemical Sciences > Organic Chemistry
Date Deposited:	07 Dec 2016 06:00
Last Modified:	07 Dec 2016 06:00
URI:	http://eprints.iisc.ac.in/id/eprint/55558

Actions (login required)

View Item