Silvana Grasso

Bio: Silvana Grasso is an academic researcher from University of Messina. The author has contributed to research in topics: Anticonvulsant Agent & AMPA receptor. The author has an hindex of 14, co-authored 43 publications receiving 857 citations. Previous affiliations of Silvana Grasso include University of Würzburg & University of Catania.

Development of Peptidomimetics with a Vinyl Sulfone Warhead as Irreversible Falcipain-2 Inhibitors

Abstract: This paper describes the synthesis of a new class of peptidomimetic cysteine protease inhibitors based on a 1,4-benzodiazepine scaffold and on an electrophilic vinyl sulfone moiety The former was introduced internally to a peptide sequence that mimics the fragment D-Ser-Gly; the latter was built on the P1-P1' site and reacts as a classical "Michael acceptor", leading to an alkylated enzyme by irreversible addition of the thiol group of the active site cysteine The introduction of the vinyl sulfone moiety has been accomplished by olefin cross-metathesis, a powerful tool for the formation of carbon-carbon double bonds New compounds 2-3 have been proven to be potent and selective inhibitors of falcipain-2, a cysteine protease isolated from Plasmodium falciparum, displaying antiplasmodial activity

Falcipain-2 inhibitors

Abstract: Malaria, particularly that one caused by Plasmodium falciparum, remains a serious health problem in Africa, South America, and many parts of Asia where it afflicts about 500 million people and is responsible for the death of more than one million children each year. The main reasons for the persistence of malaria are the emergence of resistance to common antimalarial drugs, inadequate control of mosquito vectors, and the lack of effective vaccines. Therefore, the identification and characterization of new targets for antimalarial chemotherapy are of urgent priority. This review is focused on inhibitors of falcipain-2, a cysteine protease from P. falciparum, which represents one of the most promising targets for antimalarial drug design. Falcipain-2 is a key enzyme in the life cycle of P. falciparum since it degrades hemoglobin, at the early trophozoite stage, and cleaves ankyrin and protein 4.1, the cytoskeletal elements vital to the stability of red cell membrane, at the schizont stage. The main classes of falcipain-2 inhibitors are peptides or peptidomimetics bearing the most popular pharmacophores of cysteine protease inhibitors, such as vinyl sulfones, halomethyl ketones, and aldehydes. Furthermore, many other chemotypes have been identified as inhibitors of falcipain-2, such as isoquinolines, thiosemicarbazones, and chalcones. These inhibitors represent all classes, which, to the best of our knowledge, have been disclosed in journal articles to date. © 2009 Wiley Periodicals, Inc. Med Res Rev, 30, No. 1, 136–167, 2010

Novel peptidomimetics containing a vinyl ester moiety as highly potent and selective falcipain-2 inhibitors.

Abstract: This paper describes the synthesis and biological evaluation of a new class of peptidomimetic falcipain-2 inhibitors based on a 1,4-benzodiazepine scaffold combined with various alpha,beta-unsaturated electrophilic functions such as vinyl-ketone, -amide, -ester, and -nitrile. The profile of reactivity of this class of derivatives has been evaluated and 4c, containing a vinyl ester warhead, proved to be a highly potent and selective falcipain-2 inhibitor.

Visible-Light Photocatalysis: Does It Make a Difference in Organic Synthesis?

Abstract: Visible-light photocatalysis has evolved over the last decade into a widely used method in organic synthesis. Photocatalytic variants have been reported for many important transformations, such as cross-coupling reactions, α-amino functionalizations, cycloadditions, ATRA reactions, or fluorinations. To help chemists select photocatalytic methods for their synthesis, we compare in this Review classical and photocatalytic procedures for selected classes of reactions and highlight their advantages and limitations. In many cases, the photocatalytic reactions proceed under milder reaction conditions, typically at room temperature, and stoichiometric reagents are replaced by simple oxidants or reductants, such as air, oxygen, or amines. Does visible-light photocatalysis make a difference in organic synthesis? The prospect of shuttling electrons back and forth to substrates and intermediates or to selectively transfer energy through a visible-light-absorbing photocatalyst holds the promise to improve current procedures in radical chemistry and to open up new avenues by accessing reactive species hitherto unknown, especially by merging photocatalysis with organo- or metal catalysis.

Ruthenium-based olefin metathesis catalysts bearing N-heterocyclic carbene ligands.

Abstract: N-Heterocyclic carbene (NHC) ligands, introduced as analogues to phosphines, are recently getting wide attention in the design of diverse homogeneous catalytic systems.1-6 During recent years, olefin metathesis has gained a position of increasing significance.7-9 The ruthenium complex (PCy3)2(Cl2)RudCHPh 1 (Cy ) cyclohexyl) developed by Grubbs et al.10 constitutes a highly efficient metathesis catalyst11 tolerating most functional groups. In spite of the generally superb application profile of 1, its limited stability and the low activity toward substituted double bonds are major drawbacks. The initial success of olefin metathesis has spurred the intense investigation of new catalysts for this transformation. Inter alia, the recent introduction of NHCs * To whom correspondence should be addressed. E-mail: klgrela@ gmail.com. † Polish Academy of Sciences. ‡ Warsaw University. Cezary Samojłowicz was born in 1983 in Sokołów Podlaski, Poland. He obtained his MSc Eng. degree in chemical technology from the Warsaw University of Technology, studying sigmatropic rearrangements of sulfur ylides under the supervision of Tadeusz Zdrojewski. Before moving to olefin metathesis, he conducted work on supramolecular chemistry with David Reinhoudt at Twente University. Since 2007, he is conducting his PhD study under the supervision of Karol Grela.

Recent developments in solvent-free multicomponent reactions: a perfect synergy for eco-compatible organic synthesis

Abstract: Multicomponent reactions have gained significant importance as a tool for the synthesis of a wide variety of useful compounds, including pharmaceuticals. In this context, the multiple component approach is especially appealing in view of the fact that products are formed in a single step, and the diversity can be readily achieved simply by varying the reacting components. The eco-friendly, solvent-free multicomponent approach opens up numerous possibilities for conducting rapid organic synthesis and functional group transformations more efficiently. Additionally, there are distinct advantages of these solvent-free protocols since they provide reduction or elimination of solvents thereby preventing pollution in organic synthesis “at source”. The chemo-, regio- or stereoselective synthesis of high-value chemical entities and parallel synthesis to generate a library of small molecules will add to the growth of multicomponent solvent-free reactions in the near future. In this review we summarized the results reported mainly within the last 10 years. It is quite clear from the growing number of emerging publications in this field that the possibility to utilize multicomponent technology allows reaction conditions to be accessed that are very valuable for organic synthesis. Therefore, diversity oriented synthesis (DOS) is rapidly becoming one of the paradigms in the process of modern drug discovery. This has spurred research in those fields of chemical investigation that lead to the rapid assembly of not only molecular diversity, but also molecular complexity. As a consequence multi-component as well as domino or related reactions are witnessing a new spring.