The Interactions of H2TMPyP, Analogues and Its Metal Complexes with DNA G-Quadruplexes—An Overview

Abstract

The evidence that telomerase is overexpressed in almost 90% of human cancers justifies the proposal of this enzyme as a potential target for anticancer drug design. The inhibition of telomerase by quadruplex stabilizing ligands is being considered a useful approach in anticancer drug design proposals. Several aromatic ligands, including porphyrins, were exploited for telomerase inhibition by adduct formation with G-Quadruplex (GQ). 5,10,15,20-Tetrakis(N-methyl-4-pyridinium)porphyrin (H2TMPyP) is one of the most studied porphyrins in this field, and although reported as presenting high affinity to GQ, its poor selectivity for GQ over duplex structures is recognized. To increase the desired selectivity, porphyrin modifications either at the peripheral positions or at the inner core through the coordination with different metals have been handled. Herein, studies involving the interactions of TMPyP and analogs with different DNA sequences able to form GQ and duplex structures using different experimental conditions and approaches are reviewed. Some considerations concerning the structural diversity and recognition modes of G-Quadruplexes will be presented first to facilitate the comprehension of the studies reviewed. Additionally, considering the diversity of experimental conditions reported, we decided to complement this review with a screening where the behavior of H2TMPyP and of some of the reviewed metal complexes were evaluated under the same experimental conditions and using the same DNA sequences. In this comparison under unified conditions, we also evaluated, for the first time, the behavior of the AgII complex of H2TMPyP. In general, all derivatives showed good affinity for GQ DNA structures with binding constants in the range of 106–107 M−1 and ligand-GQ stoichiometric ratios of 3:1 and 4:1. A promising pattern of selectivity was also identified for the new AgII derivative.

Transition metal(ii) complexes of halogenated derivatives of (E)-4-(2-(pyridin-2-ylmethylene)hydrazinyl)quinazoline: structure, antioxidant activity, DNA-binding DNA photocleavage, interaction with albumin andin silicostudies

“…A similar nickel complex with the simple ligand L was inactive photochemically towards plasmid DNA. 31 Comparing the literature data for the cleavage and photocleavage of the Zn complex ([Zn( L ) 2 ] 2+ ) of the non-halogenated quinazolinone ligand L , 27 which is a direct analogue to complex 2 , it seems that fluorination of the ligand at position 3′ (L 2 ) considerably enhanced the photocleavage activity using UVA and visible light ([Zn( L ) 2 ] 2+ showed ∼ 90% pDNA photocleavage at 300 μM using both UVA and visible light 27 and complex 2 100% photocleavage between 200 and 100 μM concentration using both UVA and visible light (Fig. 5)).…”

“…28–30 In addition, metal complexes that do not contain labile ligands and/or retain their stability may interact noncovalently with DNA via intercalation, groove-binding and/or electrostatic interactions. 31–33 These interactions of metal complexes with DNA may cause its cleavage, 33 whereas activation with light of appropriate wavelength may lead to photoapplications 34 that include photocatalytic hydrogen evolution, 35 creation of optical oxygen-sensitive probes, 36 photocatalysis, 37,38 DNA photocleavage 25,27,39 and photodynamic therapies. 40–42…”

Crosstalk between G-quadruplex and ROS

“…1b). Examples include PDS, acridine (BRACO-19; AS1410; RHPS4), quinacridone (BOQ1; NCQ), porphyrin (TMPyP4; NMM), and alkaloids present in traditional Chinese medicine, such as berberine, isaindigotone, quinazoline, etc [47][48][49][50]. (Table 1).…”

Arrays of graphene-quantum dots-supported DNA oligonucleotides as self-indicating porphyrin carriers

“…8–10 G4s arise from the non-canonical folding of guanine (G)-rich sequences and, from a structural point of view, comprise several stacked G-tetrads formed from the squared arrangement of four guanine nucleotides via Hoogsteen base pairing. 11,12 Depending on the nature of the surrounding monovalent cations ( e.g. Li + , Na + , K + ) also present in the medium, the G4s structures adopt different conformations, which are termed as parallel, antiparallel or hybrid.…”

“…Furthermore, the polymorphism of G4s depends on the number of chains, on the size of the oligonucleotide sequence, strand polarity and loops. 12–14…”