Magdalini Matziari has joined the Chemistry department at Xian-Jiaotong Liverpool University in 2012 as a lecturer. After having obtained a PhD degree in 2001 at the National and Kapodistrian university of Athens she worked there as a researcher and teaching assistant in the laboratory of organic chemistry. In 2006 she received the national award in Material Science of Unesco-LOréal, for In Women in Science concentrating excellence program. Magdalini works in several areas of synthetic organic chemistry with a strong emphasis on drug design and medicinal chemistry. Currently the main research interests include the development of small molecular weight inhibitors towards HIV and Hepatitis C virus enzymes, drug delivery systems and studies on organocatalysis.

Design and synthesis of modified peptide analogues with emphasis in phosphinic peptide chemistry: Phosphinic peptides are potent and selective inhibitors of Zn-metalloproteases that are involved in many physiological and pathological conditions, such as cancer, hypertension, arthritis, etc. Phosphinic inhibitors of aspartic acid proteases, such as HIV-1, have also been reported. Phosphinic peptides are not toxic, nor are they metabolized in vivo to toxic products. They act as protease inhibitors by being modified peptides that resemble the natural substrate with the difference that the peptide bond to be hydrolyzed is replaced by the stable to hydrolysis –[P(O)(OH)-CH2]- bond. The development of such compounds is considered to be a very effective approach for the study and treatment of important diseases.

Development of directly acting agents for Hepatitis: Hepatitis C virus (HCV) is the cause of Hepatitis C (HepC), an infectious disease that induces liver inflammation and cirrhosis, with no vaccine available. Until 5 years ago the treatment was based on interferon-based therapies with several drawbacks such as nausea, dyspnea, anemia, and depression leading to the development of the first generation of Directly Acting Antivirals (DAAs) which target specific enzymes of the virus. However, the treatment regimens available in the market fail to counteract all HCV genotypes. The high cost, together with the side-effects call for the development of novel DAAs that would address these drawbacks. To this end we propose to develop potent phosphinic peptide based enzyme inhibitors with increased selectivity, and lower cost compared to current therapies. Preliminary biological evaluation of these compounds shows inhibitory activity in the nM range.

Synthesis of phosphinic HIV-1 inhibitors: Lopinavir is a peptidomimetic HIV protease inhibitor that acts by binding to the catalytic site of the HIV protease thereby preventing the cleavage of viral polyprotein precursors into mature, functional proteins that are necessary for viral replication. Lopinavir is used in the therapy and prevention of human immunodeficiency virus (HIV) infection and AIDS under the trade name Kaletra, with known side-effects, such as liver problems, pancreatitis heart rhythm problems, and severe allergic reactions. Synthesis and study of phosphinic analogues of Lopinavir is considered to be an efficient alternative with reduced side-effects. One of the pilot compounds synthesized exhibited an IC50 value of 50 nM towards HIV-1.

Synthesis of carbohydrate-phosphinic conjugates as prodrugs: Use of phosphinic peptides as drugs presents some drawbacks regarding their delivery. In physiological pH values they are negatively charged and due to their polarity they are unable to penetrate the cell membranes. To overcome this problem, esters can be used as prodrugs. These esters should meet several requirements, such as chemical stability and solubility of the prodrug in the gastrointestinal tract, good permeability of the cell membranes, and finally efficient release of the drug when it reaches the target. To this end carbohydrate moieties seem to be a sound approach. A PhD thesis has been concluded in this area.

Synthesis of anti-malarial drugs: Plasmepsins are aspartic proteases that play a key role in hemoglobin degradation by the malaria parasite Plasmodium falciparum a pathogen that causes malaria, a devastating disease with estimated 650 thousand deaths per year. The development of phosphinic-based analogues and their corresponding prodrugs looks as an effective approach to inhibit plasmepsins, several analogues are under consideration.

Studies on methods for acrylic esters synthesis: Acrylic esters are useful intermediates in many synthetic routes in general and important key components in phosphinic peptide synthesis in particular. In order to achieve optimal interactions with various proteases the modifications of the core structure of the analogues should be kept to a minimum. Therefore the side chains of the phosphinic blocks should resemble the structure of natural amino acids. Since very few of them are commercially available, and some of them have been reported in the literature, studies on the development of universal methodologies that would produce all natural amino acid acrylate esters are expected to promote the development of potent and selective enzyme inhibitors.

Synthesis of phosphinic analogues of Kisspeptin-10: Kisspeptins are encoded by the KiSS1 gene in humans that was originally identified as a human metastasis suppressor gene. Kisspeptin-GPR54 signaling also plays an important role in regulating secretion of Gonadotropin-Releasing Hormone. Their dysfunction is closely related to reproductive disorders, hormone-dependent diseases including cancers, and aging. The development of kisspeptin-non-hydrolysable analogs would be an important option to design novel peptides with better therapeutic efficacy. To this end, the development of phosphinic peptide analogues is expected to be a good choice.

Development of phosphorus-based herbicides: Phosphorus based compounds are widely used as pharmaceuticals and agrochemicals such as enzyme inhibitors, antibiotics, fungicides, insecticides, pesticides, herbicides, or plant growth regulators. The bioactivity of both man-made and naturally occurring PB compounds bearing a hydrolytically stable P-C bond stems from their structural similarity to analogous phosphate esters and carboxylic acids, competing with these analogues for enzyme binding, acting thus as potent competitive inhibitors. The development of phosphinate herbicides based on Dehydrophos structure is considered, which will be studied for potency, selectivity and toxicity.

MRes Advanced Chemical Sciences Programme Director-XJTLU-2019-present

Chair of the Departmental Learning and Teaching Committee-XJTLU-2017-2019

MRes Research project coordinator-XJTLU-2013-2020

CHE112 Introductory Organic Chemistry II

CHE405 Topics in Advanced Organic Chemistry

CHE201 Intermediate Organic Chemistry

Advanced Analytical Chemistry CHE401

Measurements in Chemistry CHE206

General Chemistry CHE002

2006 , National award in Material Science of Unesco-Lapos;Or#xe9;al, for quot;In Women in Sciencequot; concentrating excellence program (2006-Greece).