Recent Insights on the Medicinal Chemistry of Metal-Based Compounds: Hints for the Successful Drug Design
Abstract:Although more complex than usually described, the anticancer action mechanism of cisplatin is based on binding to DNA. Following this line of reasoning, most the metal-based compounds discovered soon after cisplatin were designed to acting as DNA-binding agents and their pharmacological properties were thought to be correlated with this mechanism. Apart from the DNA structure, a significant number of proteins and biochemical pathways have been described as drug targets for metal-based compounds. This paper is therefore aimed at discussing the most recent findings on the medicinal chemistry of metal-based drugs. It starts illustrating the design concept behind the bioinorganic chemistry of anticancer complexes. Anticancer metallic compounds that inhibit the protein kinases are concisely discussed as a case study. The accuracy and limitations of molecular docking programs currently available to predict the binding mode of metallic complexes in molecular targets are further discussed. Finally, the advantages and disadvantages of different in vitro screenings are briefly commented.
Keywords: (source of bio-inspiration); DOCK; Gold-acridine; HAp44mT; HAp4pT; HApT; HDpT; Metal complexes; Metal-Based Compounds; Multidrug resistance/resistant; PK = Protein kinases; PROTEIN-META-LLIC COMPOUNDS; Pgp = P-glycoprotein; RR = Ribonucleotide Reductase; SAR = Structure-activity relationships; THIOSEMICARBAZO-NES; Triapine; an anticancer prototype; anti-Malarial ferrocene; biochemical mediators; bipyridine-acridine; diamino-acridine; diamino-amidineacridine; immunosuppressive; metal-based compounds; metal-based drugs; molecular docking; organometallics; pharmacological behaviours; protein kinase; ruthenium; selenoenzyme thioredoxin reductase; serendipitous process; thiosemicarbazone (centre); thiosemicarbazones; triapine
Document Type: Research Article
Publication date: November 1, 2010
- Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.