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Novel Oligopyrrole Carboxamide based Nickel(II) and Palladium(II) Salens, Their Targeting of Human G‐Quadruplex DNA, and Selective Cancer Cell Toxicity
Author(s) -
Ali Asfa,
Kamra Mohini,
Roy Soma,
Muniyappa K.,
Bhattacharya Santanu
Publication year - 2016
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201600655
Subject(s) - chemistry , dna , carboxamide , cancer cell , telomerase , stereochemistry , cell growth , biochemistry , cancer , biology , gene , genetics
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.