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

Abstract

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.

Unlocking Cu(I)-Mediated Catalytic Pathways for Efficient ROS Generation by Incorporating an Oxazole-Based Histidine Surrogate into Cu(II)–ATCUN Complexes

“…In particular, the k 2 value for Cu­(II)–GGOxa in the presence of both Asc and H 2 O 2 was approximately eight times higher than that observed in the presence of Asc only (Table ). This dependence on the redox co-reactants indicates a DNA cleavage mechanism based on redox reactions rather than hydrolysis . The accelerated DNA cleavage rates indicate that modification of the azole moiety could represent a novel approach for improving the efficiency of Cu­(II)–ATCUN complexes as artificial nucleases.…”

“…This dependence on the redox co-reactants indicates a DNA cleavage mechanism based on redox reactions rather than hydrolysis. 50 The accelerated DNA cleavage rates indicate that modification of the azole moiety could represent a novel approach for improving the efficiency of Cu(II)−ATCUN complexes as artificial nucleases.…”

Polyoxometalates as Potential Artificial Enzymes toward Biological Applications

“…[88,89] Similarly, metal complexes such as Pt II and Pd II compounds show high selectivity in the hydrolysis of peptide bonds, but require extremely low pH conditions. [90,91] Although some Co III complexes retain their hydrolytic activities at physiological pH, they are limited in their ability to cleave N-terminal peptide bonds. [92] Another example is the Cu II -cyclen complex, which exhibits high selectivity for the hydrolysis of myoglobin at two positions of Gln91-Ser92 and Ala94-Thr95 peptide bonds, however, multiple steps are required for the synthesis.…”

In vitro biological and in silico molecular docking and ADME studies of a substituted triazine-coordinated cadmium(II) ion: efficient cytotoxicity, apoptosis, genotoxicity, and nuclease-like activity plus binding affinity towards apoptosis-related proteins

“…The or L). When plasmid DNA is subject to electrophoresis, the migration rate of these conformers is in the order of form I>form III>form II (Desbouis et al 2012;Anjomshoa et al 2019;Anjomshoa and Amirheidari 2022). Figure 11A shows gel-photograph obtained from hydrolytic cleavage activity of the complex treated with pUC19 DNA at 37 °C after 1 h incubation.…”