Copper(<scp>ii</scp>)<scp>l</scp>/<scp>d</scp>-valine-(1,10-phen) complexes target human telomeric G-quadruplex motifs and promote site-specific DNA cleavage and cellular cytotoxicity

Arjmand, Farukh; Sharma, Surbhi; Parveen, Shahina; Toupet, Loı̈c; Yu, Zhen; Cowan, J. A.

doi:10.1039/d0dt01527j

Cited by 30 publications

(15 citation statements)

References 76 publications

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“… 50% decreased tumor growth of MIA-Pa-Ca2 xenografts No in vitro cyto-toxicity assay done x [ 168 ] C14 PANC-1 n.a. IC 50 : ~10 nM when irradiated with halogen light x [ 141 ] C-2028 PANC-1, MIA PaCa-2, BXpC-3, AsPC-1, Capan-2 72 h IC 50 for all cell lines < 100 nm About 80% reduced Panc-1 xenograft growth in vivo x [ 170 ] CM03 MIA PaCa-2, PANC-1 96 h IC 50 : 7 nM (MIA), 18 nM (PANC-1), reduced tumor growth by ~ 73% x [ 171 – 173 ] Copper(ii) l/d-valine-(1,10-phen) complexes (complex 1a, 1b) BxPC3, AsPC1 72 h IC 50 : ~2 μM for both complexes in both cell lines x [ 174 ] CX-3543 (Quarfloxin) MIA PaCa-2 n.a. >50% reduced tumor growth of MIA PaCa-2 xenografts x x [ 129 ] CX-5461 Gemcitabine-resistant MIA PaCa-2 (GemMIA-R3) and normal MIA-PA-Ca2 96 h GI 50 : 90.3 nM (GemMIA-R3), 88.7 nM (MIA-Pa-Ca2) x [ 175 ] MM41 MIA PaCa-2, PANC-1 96 h IC 50 : 11 nM (MIA), 3 nM (PANC-1), ~80% reduced growth of MIA PaCa-2 xenografts in vivo x [ 163 , 171 ] Naphthalene diimide ligands (compounds 3d, 3h) …”

Section: Introductionmentioning

confidence: 99%

G-quadruplexes: a promising target for cancer therapy

et al. 2021

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DNA and RNA can fold into a variety of alternative conformations. In recent years, a particular nucleic acid structure was discussed to play a role in malignant transformation and cancer development. This structure is called a G-quadruplex (G4). G4 structure formation can drive genome instability by creating mutations, deletions and stimulating recombination events. The importance of G4 structures in the characterization of malignant cells was currently demonstrated in breast cancer samples. In this analysis a correlation between G4 structure formation and an increased intratumor heterogeneity was identified. This suggests that G4 structures might allow breast cancer stratification and supports the identification of new personalized treatment options. Because of the stability of G4 structures and their presence within most human oncogenic promoters and at telomeres, G4 structures are currently tested as a therapeutic target to downregulate transcription or to block telomere elongation in cancer cells. To date, different chemical molecules (G4 ligands) have been developed that aim to target G4 structures. In this review we discuss and compare G4 function and relevance for therapeutic approaches and their impact on cancer development for three cancer entities, which differ significantly in their amount and type of mutations: pancreatic cancer, leukemia and malignant melanoma. G4 structures might present a promising new strategy to individually target tumor cells and could support personalized treatment approaches in the future.

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Section: Introductionmentioning

confidence: 99%

G-quadruplexes: a promising target for cancer therapy

et al. 2021

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“…Today, telomeric sequences are targets for anticancer therapeutics [36] , [37] , [38] . In the literature G4 oligonucleotides of human telomeric DNA is used as a substrate model for G4 DNA–binding and –cleavage studies [36] , [37] , [38] , [135] , [136] , [137] , [138] .…”

Section: Models Substrates and Instrumentations Employedmentioning

confidence: 99%

“…While agarose gel is routinely used to separate different conformations of plasmid DNA, polyacrylamide gel electrophoresis (PAGE) is applied to separate shorter nucleic acid oligos such as G4 DNA [36] , [37] , [135] , [136] , [137] , [138] .…”

Section: Models Substrates and Instrumentations Employedmentioning

confidence: 99%

Nuclease-like metalloscissors: Biomimetic candidates for cancer and bacterial and viral infections therapy

Anjomshoa

Amirheidari

2022

Coordination Chemistry Reviews

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Despite the extensive and rapid discovery of modern drugs for treatment of cancer, microbial infections, and viral illnesses; these diseases are still among major global health concerns. To take inspiration from natural nucleases and also the therapeutic potential of metallopeptide antibiotics such as the bleomycin family, artificial metallonucleases with the ability of promoting DNA/RNA cleavage and eventually affecting cellular biological processes can be introduced as a new class of therapeutic candidates. Metal complexes can be considered as one of the main categories of artificial metalloscissors, which can prompt nucleic acid strand scission. Accordingly, biologists, inorganic chemists, and medicinal inorganic chemists worldwide have been designing, synthesizing and evaluating the biological properties of metal complexes as artificial metalloscissors. In this review, we try to highlight the recent studies conducted on the nuclease-like metalloscissors and their potential therapeutic applications. Under the light of the concurrent Covid-19 pandemic, the human need for new therapeutics was highlighted much more than ever before. The nuclease-like metalloscissors with the potential of RNA cleavage of invading viral pathogens hence deserve prime attention.

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“…In general, compounds that can interfere at G4 DNA level (G4 ligands) are preferred since this interaction will result in telomerase inhibition, whose activity is up regulated in cancer cells while being silent in healthy ones. The inhibition of this enzymatic pathway will result in accumulation of shorter telomers and subsequent induction of apoptosis [ 57 ].…”

Section: Mixed Cu(ii) Phen-based Complexesmentioning

confidence: 99%

Copper(II) Phenanthroline-Based Complexes as Potential AntiCancer Drugs: A Walkthrough on the Mechanisms of Action

et al. 2021

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Copper is an endogenous metal ion that has been studied to prepare a new antitumoral agent with less side-effects. Copper is involved as a cofactor in several enzymes, in ROS production, in the promotion of tumor progression, metastasis, and angiogenesis, and has been found at high levels in serum and tissues of several types of human cancers. Under these circumstances, two strategies are commonly followed in the development of novel anticancer Copper-based drugs: the sequestration of free Copper ions and the synthesis of Copper complexes that trigger cell death. The latter strategy has been followed in the last 40 years and many reviews have covered the anticancer properties of a broad spectrum of Copper complexes, showing that the activity of these compounds is often multi factored. In this work, we would like to focus on the anticancer properties of mixed Cu(II) complexes bearing substituted or unsubstituted 1,10-phenanthroline based ligands and different classes of inorganic and organic auxiliary ligands. For each metal complex, information regarding the tested cell lines and the mechanistic studies will be reported and discussed. The exerted action mechanisms were presented according to the auxiliary ligand/s, the metallic centers, and the increasing complexity of the compound structures.

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Copper(ii)l/d-valine-(1,10-phen) complexes target human telomeric G-quadruplex motifs and promote site-specific DNA cleavage and cellular cytotoxicity

Abstract:
Chiral l-/d-valine-(1,10-phen)-Cu(ii) complexes that target G-quadruplex DNA were synthesized and thoroughly characterized. The cytotoxic activity of 1a and 1b on some of the notably important cancer cell lines was evaluated by MTT assay.

Cited by 30 publications

References 76 publications

G-quadruplexes: a promising target for cancer therapy

G-quadruplexes: a promising target for cancer therapy

Nuclease-like metalloscissors: Biomimetic candidates for cancer and bacterial and viral infections therapy

Copper(II) Phenanthroline-Based Complexes as Potential AntiCancer Drugs: A Walkthrough on the Mechanisms of Action

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Copper(ii)l/d-valine-(1,10-phen) complexes target human telomeric G-quadruplex motifs and promote site-specific DNA cleavage and cellular cytotoxicity

Abstract: Chiral l-/d-valine-(1,10-phen)-Cu(ii) complexes that target G-quadruplex DNA were synthesized and thoroughly characterized. The cytotoxic activity of 1a and 1b on some of the notably important cancer cell lines was evaluated by MTT assay.

Cited by 30 publications

References 76 publications

G-quadruplexes: a promising target for cancer therapy

G-quadruplexes: a promising target for cancer therapy

Nuclease-like metalloscissors: Biomimetic candidates for cancer and bacterial and viral infections therapy

Copper(II) Phenanthroline-Based Complexes as Potential AntiCancer Drugs: A Walkthrough on the Mechanisms of Action

Contact Info

Product

Resources

About

Abstract:
Chiral l-/d-valine-(1,10-phen)-Cu(ii) complexes that target G-quadruplex DNA were synthesized and thoroughly characterized. The cytotoxic activity of 1a and 1b on some of the notably important cancer cell lines was evaluated by MTT assay.