DNA‐Binding and Anticancer Activity of Pyrene‐Imidazolium Derivatives

Abstract

DNA-binding investigations showed that two different derivatives endowed with pyrene and imidazolium moieties, 1 and 2, strongly bind both double-stranded DNA and telomeric sequences in G-quadruplex (G4) conformation. The values of the DNA-binding constants indicate that 1 and 2 show preferential affinity for G4-DNA, of about one and two orders of magnitude, respectively. Moreover, 1 and 2 inhibit short and long-term proliferation of breast cancer cell lines in a time- and dose-dependent fashion. Remarkably, senescence assays indicate that telomeric G4-DNA is a possible biotarget for the cytotoxic activity of 2. Molecular dynamics simulations suggest that the stronger binding of 2 with G4-DNA and the related senescence induction, are a consequence of additional edge-to-face interactions with a base in the TTA loop

Comparative biological evaluation and G-quadruplex interaction studies of two new families of organometallic gold(I) complexes featuring N-heterocyclic carbene and alkynyl ligands

“…of the three compounds with the G4-DNA as previously reported for other G4-binders (Fig. 4A) [50][51][52]. The addition of AuTMX2 also causes a reduction of the shoulder at 270 nm which might suggest a slight structural change of the G4-DNA as previously observed with a nickel(II) complex [52].…”

Comprehensive Biological, Photodegradation, Density Functional Theory, and Docking Exploration of Zn(II) and Mn(II) complexes of Piroxicam

“…Coordination chemistry plays an important role in establishing a wide variety of complexes to manage ligand kinetics up to optimum therapeutic potential with improved redox potential and therapeutic activities [3–7] . During tumorigenesis, the cells’ DNA divide uncontrollably which can be the main target for anti‐cancer drugs to lessen the proliferation of these cells [8–10] . Metals encapsulated between suitable ligands impart remarkable properties of DNA cleavage through binding with DNA's negative phosphate groups [11–14] .…”

“…[3][4][5][6][7] During tumorigenesis, the cells' DNA divide uncontrollably which can be the main target for anti-cancer drugs to lessen the proliferation of these cells. [8][9][10] Metals encapsulated between suitable ligands impart remarkable properties of DNA cleavage through binding with DNA's negative phosphate groups. [11][12][13][14] Besides inherent anti-cancer properties, Non-ster-oidal anti-inflammatory drugs (NSAIDs) also exhibit a synergistic role with anti-tumor drugs and involve in cell death through apoptosis.…”

Annulation of Perimidines with 5-Alkynylpyrimidines en Route to 7-Formyl-1,3-Diazopyrenes

“…Major advances were made in the development of pyrene-based fluorescent probes [ 11 ] for the analytical detection of copper [ 12 , 13 ] and other heavy metals [ 13 ], as well as picric acid [ 14 ]. These versatile synthons also possess a great intercalating ability to selectively bind to DNA in cellular nuclei [ 15 , 16 ]. The undisputed advantages of pyrene derivatives are outweighed by one significant drawback–their low solubility in common organic solvents—which complicates synthesis of advanced synthetic precursors for the manufacturing of photosensors and electronic devices.…”