Current Topics in Medicinal Chemistry - Volume 11, Issue 22, 2011

Although the single-target approach still remains the current drug discovery strategy in medicinal chemistry for the development of new bioactive molecules, there is increasing recognition that this is the main reason of a lack of a successful therapy for the treatment of multifactorial, complex diseases such as cancer or Alzheimer. Thus, an alternative approach, routinely named the “Multi-target Directed Ligand” (MTDL), based Read More

Progresses in medicinal chemistry over the last few years have focused on the design and synthesis of hybrid compounds, molecules encompassing in a single scaffold two pharmacophores from known entities endowed with well established biological activities. The interest in this topic is related to the increasing emphasis on the identification of the different factors involved in a number of disorders, such as the complex multifact Read More

The occurrence of orthosteric and allosteric binding sites is a characteristic common feature of several acetylcholine- binding proteins, like acetylcholinesterase or the nicotinic and muscarinic acetylcholine receptors. These proteins are involved in a number of neurological disorders, such as Alzheimer's disease, and represent important therapeutic targets for the development of heterodimeric ligands addressing both Read More

The development of ligands that as single chemical entities are able to modulate multiple epigenetic targets simultaneously (designed epigenetic multiple ligands) is still in its infancy. We are witnessing some advances with combinations of the fused or linked pharmacophores of an epi-drug and other anticancer agents. More recently, however, a very promising approach has been developed in which a single chemical entity Read More

Playing a pivotal role in the metabolism of neurotransmitters in the central nervous system, the mitochondrial enzymes monoamine oxidases A and B (MAO A and B) have been for long studied as drug targets for neurodegenerative and neurological diseases. MAO inhibitors (MAOIs) are clinically used to treat Parkinson's disease and depression by blocking the degradation of neuroactive catecholamines and providing a symptoma Read More

Multitarget agents directed at selected molecular targets involved in the pathogenic cascade of Alzheimer's disease (AD) have been increasingly sought after in recent years, with the aim of achieving enhanced therapeutic efficiency with respect to single-target drugs and drug candidates. At the same time, much attention has been devoted to identifying high quality pharmacological tools to help explore the molecular mecha Read More

The synthesis and the pharmacological evaluation of 1,8-naphthyridine derivatives and related compounds as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), as well as voltage-dependant Ca2+ channels (VDCC) modulators of are summarized. These compounds are closely related to the anticholinesterasic tacrine and the well-known Ca2+-antagonists 1,4-dihydropyridines. They were obtained fro Read More

Of the tropical diseases, trypanosomiases and leishmaniases should most concern the pharmaceutical community because of their high prevalence in developing countries and the lack of effective drug treatments. Despite this, they have not historically received much attention in terms of investment and research effort, nor do they now. In very recent years, thanks to the involvement of several nonprofit organizations, the Read More

Thromboembolic disorders are still the leading causes of morbidity and mortality in developed societies. Therefore, prophylaxis and treatment of arterial and venous thrombosis are among the main therapeutic challenges nowadays. Simultaneous action on several targets involved in pathology of thrombosis offers potential advantages compared to existing drugs which were developed as selective modulators of single Read More