Mini Reviews in Medicinal Chemistry - Volume 11, Issue 4, 2011

Dr. Patrice Talaga (1962-2010) Patrice Talaga was born in Stiring-Wendel, France in 1962. He studied chemistry at the University of Strasbourg where he completed his Ph.D. related to the synthesis and biological testing of allergen- (non)peptides conjugates for the treatment of contact dermatitis, in 1989 under the supervision of the late Professor Claude Benezra. He also obtained a master degree in drug design from Lille II University in 1995. He began his career at Hoechst AG (now part of Sanofi-Aventis) working on peptidomimetics and nonnatural peptides. After a 2 years stay in Germany, he decided to move to Belgium where he started as a medicinal chemist at UCB Pharma in 1991. In his early days at UCB, Dr. Talaga took an active part in the initiation of combinatorial chemistry which then became a key unit. Very rapidly though, he showed a great interest in the relationships the chemistry department could link with the external world, universities and CRO's in particular. That interest, together with an exquisite scientific expertise that went well beyond chemistry, allowed him to create a small team responsible for external collaborations and contracts. His scientific skills, as well as an extraordinary capacity to engage in respectful relationships characterized by mutual trust, helped him to quickly establish an impressive network which he has developed and enriched throughout the years. The success of several drug discovery collaborations resulted in a well-deserved international recognition in the field of outsourcing. His pronounced interests for new trends and hot topics in the pharmaceutical industry led him recently to actively foster “open innovation” partnerships in the chemistry department, a domain for which he was also starting to be widely recognized. Dr. Talaga also acquired a particular expertise in the field of Parkinson's disease and epilepsy. His personal interests were nevertheless biased towards cognitive disorders. His passion for innovation in those fields allowed him to propose several new therapeutic projects, one of them being currently in Phase I for the symptomatic treatment of Alzheimer's disease. He was a referee for numerous journals and an esteemed member of the editorial board of several international journals such as “Mini-Reviews in Medicinal Chemistry”, for which he served as co-editor-in-chief, “Future Medicinal Chemistry” or “Chimie Nouvelle”. He acted as an expert for the European Community in the framework of FP6 and FP7 calls and was also the leader of a FP7-IAPP project around foldamers. Dr. Talaga was a respected scientist with an impressive publication list, being the author or co-author of about 40 papers and patents, and has been invited at several key symposia. The unexpected death of Dr. Talaga last December has devastated all the people who had the chance to work or do business with him or simply meet him. UCB's chemistry department as well as the entire scientific community have lost a great colleague and one of their most human, open-minded and innovative chemist. SELECTED PAPERS Talaga, P. “The future of pharmaceutical R&D: Somewhere between open and reverse innovation ?” Future Med. Chem. 2010, 2, 1399-1403 Talaga, P. “Open Innovation: share or die...” Drug Discovery Today 2009, 14, 1003-5 Talaga, P. “β-Amyloid aggregation inhibitors for the treatment of Alzheimer's disease: dream or reality ?” Mini Reviews Med. Chem. 2001, 1, 175-186

Previous studies have shown that cellular function depends on rod-like membrane proteins, among them Bin/Amphiphysin/Rvs (BAR) proteins may curve the membrane leading to physiologically important membrane invaginations and membrane protrusions. The membrane shaping induced by BAR proteins has a major role in various biological processes such as cell motility and cell growth. Different models of binding of BAR domains to the lipid bilayer are described. The binding includes hydrophobic insertion loops and electrostatic interactions between basic amino acids at the concave region of the BAR domain and negatively charged lipids. To shed light on the elusive binding dynamics, a novel experiment is proposed to expand the technique of single-molecule AFM for the traction of binding energy of a single BAR domain.

In the absence of crystallographic data, NMR has emerged as the best way to define protein-ligand interactions. Using NMR experiments based on magnetization transfer, one can sort bound from unbound molecules, estimate the dissociation constant, identify contacts implied in the binding, characterize the structure of the bound ligand and conduct ligand competition assays.

Epidemiological studies have revealed that a diet rich in plant-derived foods has a protective effect on human health. Identifying bioactive dietary constituents is an active area of scientific investigation that may lead to new drug discovery. Kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is a flavonoid found in many edible plants (e.g. tea, broccoli, cabbage, kale, beans, endive, leek, tomato, strawberries and grapes) and in plants or botanical products commonly used in traditional medicine (e.g. Ginkgo biloba, Tilia spp, Equisetum spp, Moringa oleifera, Sophora japonica and propolis). Some epidemiological studies have found a positive association between the consumption of foods containing kaempferol and a reduced risk of developing several disorders such as cancer and cardiovascular diseases. Numerous preclinical studies have shown that kaempferol and some glycosides of kaempferol have a wide range of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, anticancer, cardioprotective, neuroprotective, antidiabetic, anti-osteoporotic, estrogenic/antiestrogenic, anxiolytic, analgesic and antiallergic activities. In this article, the distribution of kaempferol in the plant kingdom and its pharmacological properties are reviewed. The pharmacokinetics (e.g. oral bioavailability, metabolism, plasma levels) and safety of kaempferol are also analyzed. This information may help understand the health benefits of kaempferol-containing plants and may contribute to develop this flavonoid as a possible agent for the prevention and treatment of some diseases.

Comparing with the wide usage of ferrocene in novel materials, ferrocene was unusually applied to be a structural feature in designing drugs even though some researchers pointed out that ferrocene and its derivatives possessed potential pharmacological applications. This was due to that low polarity limited bioavailability of ferrocene in vivo. Since ferrocene was inert to the oxidation at atmosphere, it was deduced that synthetic derivatives of ferrocene may be a novel kind of antioxidant, in which other organic groups may enhance the bioavailability of ferrocene, or large conjugated system formed among ferrocenyl and other organic groups may increase the antioxidant effectiveness. Thus, synthetic derivatives of ferrocene were divided into nonconjugated and conjugated ones in this review. For nonconjugated ferrocenyl derivatives, carbon chain or simple group attached one or two cyclopentadienyl rings in ferrocene to form a novel molecule with ferrocenyl group. The aim of synthesis of nonconjugated ferrocenyl compounds was to increase the bioavailability of ferrocene in vivo. On the other hand, the conjugated ferrocenyl derivatives referred to introduce other group to form a conjugated system with the cyclopentadienyl ring in ferrocene. The large conjugated system was beneficial for the single electron to dispense among the whole molecule while forming radicals, and enhanced the antioxidant capacity of the whole molecule. This review summarized the potential usage of ferrocene in antioxidants.