Recent advances in metallodrug-like molecules targeting non-coding RNAs in cancer chemotherapy

摘要

New drug discovery strategies are emerging at a rapid pace to combat the threat of mortality caused by various chronic diseases viz., HIV-AIDS, respiratory infections and cancers. The therapeutic intervention is necessary for synthesizing robust pharmaceuticals and to unlock the mechanistic aspects of pathogens involved in diseases. These therapeutic regimes have diverted from traditional target DNA to new exciting novel targets viz., structured proteins, enzyme receptors, ribonucleoprotein (RNP) particles and non coding RNAs. RNA has much attractive prospectus as an antitumor therapeutic target being involved in many essential biochemical, genetic and epigenetic functions of the cell. The structural flexibility of RNA both in secondary and tertiary structure owing to which selective binding based on structures rather than sequence is possible while RNP particles have exhibited reasonable therapeutic success in the antibacterial area. RNA was much ignored and underexploited target due to difficulty in characterisation and unavailability of sensitive biophysical/biochemical techniques to study its intricate threedimensional folds. However, recent developments have provided valuable insights into RNA targets, and its binding abilities, the small molecule RNA-based drugs have emerged, and many antitumor lead compounds targeted to RNA including organic dyes, intercalative cations, aminoglycoside antibiotics and inorganic metal complexes were isolated, and some of them have reached clinical trial phases in drug discovery. Interestingly, the development of high-resolution RNA structural analysis, using both X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy has clearly made a profound impact in this area. In the present review, we are looking at more naive options of modulating drug discovery strategies involving metallodrugs derived from transition metal ions which are targeted to ncRNAs. Metal complexes exhibit diversity in size and structure beyond the geometries of carbon, possess photo physical and electrochemical properties and therefore are considered as an important class of structure selective binding agents for nucleic acids. Herein, we describe innovative rational designs of metallodrugs targeted to non-coding RNA structures and their future biological prospectus in drug design. (C) 2019 Elsevier B.V. All rights reserved.