Editorial: Multi-Target-Directed Ligands (MTDL) as Challenging Research Tools in Drug Discovery: From Design to Pharmacological Evaluation

Abstract

The philosophy “one molecule-one target-one disease” was the dominant approach in medicinal chemistry for several decades up till the end of the twentieth century. This strategy was based on the identification and optimization of small chemical entities able to recognize specifically one target, believed to be fully responsible for a certain disease. The aim of the “one drug-one target” approach was to find bioactive compounds endowed with a limited risk of off-target properties, many times responsible for drug side-effects. This philosophy started to change in the last 20 years due to the emergent growing awareness that drugs designed to act on individual molecular targets are usually inadequate for multigenic diseases such as cancer, neurodegenerative, and infectious diseases (Ramsay et al., [2]). System biology and omic sciences recently enriched the knowledge of the complex world underlying their pathogenesis, depicting the importance of networked signaling pathways and suggesting multi-target therapeutics as potentially more advantageous than mono-therapies. Nowadays, so called “drug-cocktails” are often the only available approaches to pharmacologically treat many of these pathologies, with concerns related to drug-drug interactions as well as to patients' compliance. Hence, it is appropriate and relevant to search for novel bioactive compounds able to combine in one molecule multi-target properties, according to the paradigm of “network pharmacology” (Hopkins, [1]). Therefore, a special issue dedicated to collect research activities from critical areas for the development of novel multi-target-directed ligands (MTDL) through the close cooperation among pharmacologists, biochemists, medicinal chemists, and toxicologists, has been proposed. This research topic should collect new approaches developed to overcome the main issues faced by medicinal chemists in the design, synthesis, and biological evaluation of these promising, but extremely challenging, new chemical entities. The first is the identification of new MTDL derived either from natural sources or synthetic procedures.