Current Bioactive Compounds - Volume 6, Issue 4, 2010

This issue is dedicated to scientists belonging to either or both the fields of heterocyclic and medicinal chemistry. Nowadays, pharmaceutical industries are more and more dedicating their research towards different use or applications of the same molecule rather than towards the development of new drugs. In the latter decades, in fact, the time which is necessary since a given molecule is synthesized to when it is approved as a drug has significantly increased. Therefore, the development of time-saving methodologies such as combinatorial chemistry and computationally driven drug design has attracted the interest of several organic and medicinal chemists. Many of the molecules tested in-vitro through HTS (High Throughput Screening) belong to the class of commercial or easy to achieve compounds. On the other hand, in-silico screened compound are usually taken from chemical structure databases containing millions of “virtual” samples which are stripped down to thousands and then hundreds or tenths, preferring exhisting non-patented molecules over new-to-synthesize targets. In this context, hidden treasures such as actual compound libraries from academic or research center's synthetic laboratories are often forgotten. This underestimation of the potential (bioactive) value of a given series of non-commercially available compounds is mainly due to the lack of “communication” between chemists interested in new synthetic methodologies or mechanistic investigations and chemists involved in developing new drugs. Such a gap is particularly noticeable by heterocyclic chemists since, of course, many drugs contain a heterocyclic core. This issue aims, therefore, at tying a few strings between laboratories involved in basic knowledge (i.e. Synthesis and Reactivity) and in biological/medicinal application of heterocycles, particularly azoles. In this context, the contributions in this issue are heterocycle-centered rather than application-centered, which means that for a given class of heterocycles a series of recent developments in various applications will be discussed. This approach will be helpful for both synthetic chemists and pharmaceutical researchers: the former, who is aware of the type of structure he or she is able to obtain, will direct the synthesis towards a given compound for a given application; the latter will be given a panorama of recent applications for each group of structures, opening the way to further development. As far as single heterocyclic nucleus are concerned, the contributions include triazoles, discussed in Chapter 1, and thiadiazoles, discussed in Chapter 2, while oxadiazoles, particularly 1,2,4-oxadiazoles, were not included since their bioactivity has been recently reviewed. The recent bioactivity of the benzocondensated derivatives of all the three kind of heterocycles mentioned above has been discussed in Chapter 3. Finally, natural bioactive compounds containing azole moieties have been discussed in Chapter 4. Although many of the azole moieties presented in the latter contribution contain two, rather than three, heteroatoms, the reported structures will give several inputs to the synthetic chemist about which natural framework could be the most appropriate one to insert other isosteric azoles with different electronic properties and potentally new bioactivity.

Scientists have extensively explored new synthetic routes in order to obtain 1,2,3- and 1,2,4-triazoles as they represent a very interesting class of compounds due to their wide range of biological activities such as antitumor, antiinflammatory, analgesic, antifungal, antibacterial, antiviral, etc. This mini review reports the synthesis and the biological activities of compounds containing a triazole moiety published since 2007. No attempt is made to provide a comprehensive literature overview, our aim is to highlight some more recent examples of synthetic biological active compounds. In particular, we focus on the applications of “click reactions” that allow the regioselective synthesis of 1,2,3 triazoles as well as on bioactive 1,2,4 triazoles obtained by classic and improved synthetic methodologies. Moreover bioactivity of glycoconjugated, and metal complexes with triazole as ligands are herein discussed, fused ring heterocycles have not been taken into account. Where possible some comments on structure-activity relationships are referred.

The aim of the review is the coverage of recent open literature (2007-2009) on thiadiazole-containing bioactive compounds. Review's sections are organized on the basis of the biological activities (antitumorals, antibacterial, antifungal agents, analgesics, etc.).

The aim of this review is the coverage of recent literature (2007-2009) on bioactive compounds containing benzoxadiazole, benzothiadiazole and benzotriazole nucleus, as central core as well as substituent in the context of SAR studies. Review's sections are organized on the basis of heterocycle contained in drug structure and subdivided for represented main activities (Antitumorals, antiviral, antibacterial, antifungal agents, analgesics, etc.).

The aim of the present review is to portray a concise account of the isolation, chemistry and bioactivity of azoles-containing natural products discovered during the last few years with a special emphasis on those compounds with a new structural motif. The material will be classified on a structural basis starting from simple monocycle-containing open chain molecules to the complex polyazole-containing, medium- and large-sized macrolides. Details on the isolation procedures and on the biological targets and activities will be given. Molecules in which azoles are present as part of standard amino-acids and nucleobases will not be considered.