Reece G. Kenny

Bio: Reece G. Kenny is an academic researcher from Royal College of Surgeons in Ireland. The author has contributed to research in topics: Vorinostat & Belinostat. The author has an hindex of 3, co-authored 4 publications receiving 343 citations.

Toward Multi-Targeted Platinum and Ruthenium Drugs-A New Paradigm in Cancer Drug Treatment Regimens?

Abstract: While medicinal inorganic chemistry has been practised for over 5000 years, it was not until the late 1800s when Alfred Werner published his ground-breaking research on coordination chemistry that we began to truly understand the nature of the coordination bond and the structures and stereochemistries of metal complexes. We can now readily manipulate and fine-tune their properties. This had led to a multitude of complexes with wide-ranging biomedical applications. This review will focus on the use and potential of metal complexes as important therapeutic agents for the treatment of cancer. With major advances in technologies and a deeper understanding of the human genome, we are now in a strong position to more fully understand carcinogenesis at a molecular level. We can now also rationally design and develop drug molecules that can either selectively enhance or disrupt key biological processes and, in doing so, optimize their therapeutic potential. This has heralded a new era in drug design in which we a...

Platinum(IV) Prodrugs – A Step Closer to Ehrlich's Vision?

Abstract: The concept of the 'magic bullet', a medicine designed to hit a specific biological target, was pioneered by Paul Ehrlich, the father of chemotherapy some 100 years ago. Building on Ehrlich's vision, we have endeavoured to showcase how targeted Pt(IV) prodrugs may be exploited to not only reduce systemic toxicities associated with modern day chemotherapeutics including classical Pt(II) drugs but also how these prodrugs may overcome resistance issues that have plagued many chemotherapeutic regimes. A summary of advances in this field over the past decade is provided with an emphasis on Pt(IV) prodrugs that not only target DNA but also enzymes, proteins, peptides and hormones. Synthetic strategies for accessing Pt(IV) chemistry are also provided.

CHAPTER 1:Enhancing the Therapeutic Potential of Platinum-based Anticancer Agents by Incorporating Clinically Approved Drugs as Ligands

Abstract: In this chapter, we have endeavoured to showcase how some clinically approved drugs may be exploited as potential ligands when designing new metallodrugs to treat cancer. Interestingly, while there is a sound rationale behind repurposing existing drugs, those to date that have been tethered to platinum(ii) and platinum(iv) centres have not been chosen for this purpose. Rather, they have been selected because these drugs, in their own right, have exhibited potent anticancer activities albeit some are in clinical use for other indications. This chapter will provide an overview of some interesting platinum(ii) and platinum(iv) complexes incorporating a selection of clinically approved drugs or derivatives thereof as ligands. These complexes may form the basis of a new drug class which may offer advantages over existing therapeutic regimens.

Toward Multi-Targeted Platinum and Ruthenium Drugs-A New Paradigm in Cancer Drug Treatment Regimens?

Abstract: While medicinal inorganic chemistry has been practised for over 5000 years, it was not until the late 1800s when Alfred Werner published his ground-breaking research on coordination chemistry that we began to truly understand the nature of the coordination bond and the structures and stereochemistries of metal complexes. We can now readily manipulate and fine-tune their properties. This had led to a multitude of complexes with wide-ranging biomedical applications. This review will focus on the use and potential of metal complexes as important therapeutic agents for the treatment of cancer. With major advances in technologies and a deeper understanding of the human genome, we are now in a strong position to more fully understand carcinogenesis at a molecular level. We can now also rationally design and develop drug molecules that can either selectively enhance or disrupt key biological processes and, in doing so, optimize their therapeutic potential. This has heralded a new era in drug design in which we a...

Metal complexes as a promising source for new antibiotics.

Abstract: There is a dire need for new antimicrobial compounds to combat the growing threat of widespread antibiotic resistance. With a currently very scarce drug pipeline, consisting mostly of derivatives of known antibiotics, new classes of antibiotics are urgently required. Metal complexes are currently in clinical development for the treatment of cancer, malaria and neurodegenerative diseases. However, only little attention has been paid to their application as potential antimicrobial compounds. We report the evaluation of 906 metal-containing compounds that have been screened by the Community for Open Antimicrobial Drug Discovery (CO-ADD) for antimicrobial activity. Metal-bearing compounds display a significantly higher hit-rate (9.9%) when compared to the purely organic molecules (0.87%) in the CO-ADD database. Out of 906 compounds, 88 show activity against at least one of the tested strains, including fungi, while not displaying any cytotoxicity against mammalian cell lines or haemolytic properties. Herein, we highlight the structures of the 30 compounds with activity against Gram-positive and/or Gram-negative bacteria containing Mn, Co, Zn, Ru, Ag, Eu, Ir and Pt, with activities down to the nanomolar range against methicillin resistant S. aureus (MRSA). 23 of these complexes have not been reported for their antimicrobial properties before. This work reveals the vast diversity that metal-containing compounds can bring to antimicrobial research. It is important to raise awareness of these types of compounds for the design of truly novel antibiotics with potential for combatting antimicrobial resistance.

NAMI-A and KP1019/1339, Two Iconic Ruthenium Anticancer Drug Candidates Face-to-Face: A Case Story in Medicinal Inorganic Chemistry

Abstract: NAMI-A ((ImH)[trans-RuCl4(dmso-S)(Im)], Im = imidazole) and KP1019/1339 (KP1019 = (IndH)[trans-RuCl4(Ind)2], Ind = indazole; KP1339 = Na[trans-RuCl4(Ind)2]) are two structurally related ruthenium(III) coordination compounds that have attracted a lot of attention in the medicinal inorganic chemistry scientific community as promising anticancer drug candidates. This has led to a considerable amount of studies on their respective chemico-biological features and to the eventual admission of both to clinical trials. The encouraging pharmacological performances qualified KP1019 mainly as a cytotoxic agent for the treatment of platinum-resistant colorectal cancers, whereas the non-cytotoxic NAMI-A has gained the reputation of being a very effective antimetastatic drug. A critical and strictly comparative analysis of the studies conducted so far on NAMI-A and KP1019 allows us to define the state of the art of these experimental ruthenium drugs in terms of the respective pharmacological profiles and potential clinical applications, and to gain some insight into the inherent molecular mechanisms. Despite their evident structural relatedness, deeply distinct biological and pharmacological profiles do emerge. Overall, these two iconic ruthenium complexes form an exemplary and unique case in the field of medicinal inorganic chemistry.