Design, Synthesis, and Evaluation of Multi-Target Ligands

Dear Colleagues,

The classic “one drug, one target” therapeutic approach, due to pharmacogenomic effects and variable key biological pathways, often results in unpredictable individual drug responses. A good alternative, especially in the case of a complex disorder or drug resistance, seems to be single chemical compounds capable of acting simultaneously. Some drugs known in medical practice for a long time, now turn out to be effective in the treatment of completely different diseases, thus they can be considered multi-directional or multi-targeted drugs. The design of multi-target drug is somewhat reminiscent of a master key system, where the same key opens many different locks, and the functionality of the key is determined by the individual and common parts of the key blade. By analogy, this kind of drug is designed to bind multiple targets, so it should fit into multiple protein pockets, either in the same protein or different proteins. Designing entirely new multi-target drug, although it seems very easy in concept, is in fact a complex task. The development of various strategies based on ligands or structures, experimental techniques, in silico, and artificial intelligence methods, increase the chances of success in this field. Computer-aided drug design based on modern techniques such as molecular docking, which accelerates screening, and molecular dynamics simulations, which add a "degree of flexibility" to structures, provide insight into the mechanism of ligand-target binding. In silico and artificial intelligence methods predict the physicochemical profiles of ligands and reveal structure-activity relationships. Both of these classes of methods significantly facilitate ligand modelling, analogue design and optimisation of leading compounds. Today, more than one twentieth of all medicines approved annually by the Food and Drug Administration are multi-target medicines. Most of them are proving particularly attractive for multifactorial debilitating diseases such as cancer, cardiovascular diseases neurological and neurodegenerative diseases, diabetes or viral infections,where combined action produces a much faster and better therapeutic effect. Advances in the understanding of the molecular structure, stability, strength and nature of drug binding in relation to their biological activity are the basis for improving drugs and setting new directions for synthesis.

In this Special Issue, we welcome submissions on recent advances in the design, synthesis, evaluation and applications of multi-target drugs. 

Prof. Dr. Jolanta Natalia Latosińska
Guest Editor

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• multi-target drugs
• in silico methods
• molecular docking
• molecular dynamics simulations
• mechanism of ligand-target binding