Multi-target-directed-ligands acting as enzyme inhibitors and receptor ligands

Abstract In this review, we present the latest advances in the field of multi-target-directed ligand (MTDL) design for the treatment of various complex pathologies of multifactorial origin. In particular, latest findings in the field of MTDL design targeting both an enzyme and a receptor is presented for different diseases such as Alzheimer's disease (AD), depression, addiction, glaucoma, non-alcoholic steatohepatitis and pain and inflammation. The ethology of the diseases is briefly described, with special emphasis on how the MTDL can evolve into novel therapies that replace the classic pharmacological dogma “one target one disease”. Considering the current needs for therapy adherence improvement, it is exposed as from the medicinal chemistry, different molecular scaffolds are studied. With the use of structure relationship studies and molecular optimization, new hybrid molecules are generated which can improve biological properties such as selectivity and potency.