Coumarins, also known as benzopyrones, are present in remarkable amounts in plants, although their presence has also been detected in microorganisms and animal sources. The structural diversity found in this family of compounds led to the division into different categories, from simple coumarins to many other kinds of policyclic coumarins, such as furocoumarins and pyranocoumarins. Simple coumarins and analogues are a large class of compounds that have attracted their interest for a long time due to their biological activities: they have shown to be useful as antitumoural, anti-HIV agents and as CNSactive compounds. Furthermore, they have been reported to have multiple biological activities (anticoagulant, anti-inflammatory), although all these properties have not been evaluated systematically. In addition, their enzyme inhibition properties, antimicrobial and antioxidant activities are other foremost topics of this field of research. The present work is to survey the information published or abstracted from 1990 till 2003, which is mainly related to the occurrence, synthesis and biological importance of simple coumarins and some analogues, such as biscoumarins and triscoumarins. Data are also highlighted, concerning the development of new synthetic strategies that could help in drug design and in the work on SAR or QSAR.

Background Drug–drug interactions (DDIs) are responsible for many serious adverse events; their detection is crucial for patient safety but is very ch

The numerical encoding of chemical structure with Topological Indices (TIs) is currently growing in importance in Medicinal Chemistry and Bioinformatics. This approach allows the rapid collection, annotation, retrieval, comparison and mining of chemical structures within large databases. TIs can subsequently be used to seek quantitative structure-activity relationships (QSAR), which are models connecting chemical structure with biological activity. In the early 1990s, there was an explosion in the introduction and definition of new TIs. The Handbook of Molecular Descriptors by Todeschini and Consonni lists more than 1500 of these indices. At the end of the last century, researchers produced a large number of TIs with essentially the same advantages and/or disadvantages. Consequently, many researchers abandoned the definition of TIs for a time. In our opinion, one of the problems associated with TIs is that researchers aimed their efforts only at the codification of chemical connectivity for small-sized drugs. As a consequence, recently it seems that we have arrived at “Fukuyamas End of History in TIs definition”. In the work described here, we review and comment on the “quo vadis” and challenges in the definition of TIs as we enter the new century. Emphasis is placed on new chiral TIs (CTIs), flexible TIs for unifying QSAR models with multiple targets, topographic indices (TPGIs), TIs for DNA and protein sequences, TIs for 2D RNA structures, TPGIs and drug-protein or drug-RNA quantitative structure-binding relationship (QSBR) studies, TIs to encode protein surface information and TIs for protein interaction networks (PINs).

The scope of this review encompasses the importance of furocoumarins and the most important developments in this field that have been made in recent years, with particular emphasis placed on the aspects related to medicinal chemistry. A concise and exhaustive overview is given regarding the methods used for the synthesis of these compounds, new furocoumarins isolated from natural sources, and the most significant biological properties associated with these molecules. The section describing the synthetic methods is organized on the basis of the key step used for the formation of the two different oxygenated rings. In this respect there are three possibilities: (i) formation of the furan ring onto the coumarin, (ii) formation of the pyrone ring onto the benzofuran and (iii) the simultaneous formation of both oxygenated rings onto a benzene unit. The most recent preparative approaches are discussed along with modifications or improvements to methods that, though not particularly new, are still commonly used. The recently discovered natural furocoumarins are focused and presented in tables that provide information about its structure and source. The discussion of the biological importance of furocoumarins mainly focuses on their more relevant applications in photochemotherapy, but also provides examples of their versatility in a range of applications in the fields of biology and pharmacology.