Chromones are a group of naturally occurring compounds that are ubiquitous in nature, especially in plants. The word chromone is derived from the Greek word chroma, meaning “color”, which point out that many chromone derivatives can exhibit a diversity of colors.This work was supported by the Foundation for Science and Technology (FCT), Portugal (projects PTDC/QUI-QUI/113687/2009 and PEst-C/QUI/UI0081/2013). A.G. (SFRH/BD/43531/2008) and M.J.M. (SFRH/BD/61262/2009) thank FCT for grants

Site-selective chemical conjugation of synthetic molecules to proteins expands their functional and therapeutic capacity. Current protein modification methods, based on both synthetic and biochemical technologies, can achieve site-selectivity, but these techniques often require extensive sequence engineering or are restricted to the N- or C-terminus. Here we show the computer-assisted design of sulfonyl acrylate reagents for the modification of a single lysine residue on native protein sequences. This feature of the designed sulfonyl acrylates, together with the innate and subtle reactivity differences conferred by the unique local microenvironment surrounding each lysine, contribute to the observed regioselectivity of the reaction. Moreover, this site-selectivity was predicted computationally, where the lysine with the lowest pKa was the kinetically favoured residue at slightly basic pH. Chemoselectivity was also observed as the reagent reacted preferentially at lysine, even in those cases when other nucleophilic residues such as cysteine were present. The reaction is fast and proceeds using a single molar equivalent of the sulfonyl acrylate reagent under biocompatible conditions (37 ºC and pH 8.0). This technology was demonstrated by the quantitative and irreversible modification of five different proteins including the clinically used therapeutic antibody Trastuzumab without prior sequence engineering. Importantly, their natural secondary structure and functionality is retained after the modification. This regioselective lysine modification method allows for further bioconjugation through aza-Michael addition to the acrylate electrophile that is generated by spontaneous elimination of methanesulfinic acid upon lysine labelling. We showed that a protein and an antibody conjugate bearing a site-specifically installed fluorophore at lysine could be used for selective imaging of apoptotic cells and detection of Her2+ cells, respectively. This simple and robust method does not require genetic engineering and may be generally used for accessing diverse, well-defined protein conjugates for basic biology and therapeutic studies.

Maleimides remain the reagents of choice for the preparation of therapeutic and imaging protein conjugates despite the known instability of the resulting products that undergo thiol-exchange reactions in vivo. Here we present the rational design of carbonylacrylic reagents for chemoselective cysteine bioconjugation. These reagents undergo rapid thiol Michael-addition under biocompatible conditions in stoichiometric amounts. When using carbonylacrylic reagents equipped with PEG or fluorophore moieties, this method enables access to protein and antibody conjugates precisely modified at pre-determined sites. Importantly, the conjugates formed are resistant to degradation in plasma and are biologically functional, as demonstrated by the selective imaging and detection of apoptotic and HER2+ cells, respectively. The straightforward preparation, stoichiometric use and exquisite cysteine selectivity of the carbonylacrylic reagents combined with the stability of the products and the availability of biologically relevant cysteine-tagged proteins make this method suitable for the routine preparation of chemically defined conjugates for in vivo applications.

Chalcones are one of the major classes of naturally occurring compounds. A large number of synthetic routes have been reported for the synthesis of chalcones, the most classical and general being the Claisen-Schmidt condensation. Chalcones and their derivatives have a huge importance in medicinal chemistry, displaying a wide range of important pharmacological activities. The authors provide an overview of the recent scientific reports describing the obtention and study of new chalcones. The review emphasizes the rationale behind the natural sources, the discovery, the design, the synthesis, the biological activities and the study of structure-activity relationships of the new chalcone derivatives. The article is based on the literature published from June 2011 - 2014 related to the development of this family of compounds. The patents presented in this review have been collected from multiple electronic databases including Scifinder, Espacenet and Mendeley. Although a great number of extracts containing chalcones have been published in bibliographic sources, the potential of this scaffold could be deeply studied in many different areas in which almost nothing has been described. A lot of work should be done to reach the potency and safety requirements needed to develop new chemical entities as new drugs.

Coumarins — An Important Class of Phytochemicals | InTechOpen, Published on: 2015-09-30. Authors: Maria João Matos, Lourdes Santana, Eugenio Uriarte, et