Projects per year
Personal profile
Personal profile
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.
Research interests
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.
Experience
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
Teaching
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
Awards and honours
2006 , National award in Material Science of Unesco-Lapos;Or#xe9;al, for quot;In Women in Sciencequot; concentrating excellence program (2006-Greece).
Expertise related to UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
Related documents
Education/Academic qualification
Ph.D. , in Chemistry, National and Kapodistrian University of Athens (NKUA), Athens, Greece, - 2001
MSc , in Organic Chemistry, National and Kapodistrian University of Athens (NKUA), Athens, Greece, - 1999
Other , Chemistry degree, University of Ioannina, Department of Chemistry, Greece, - 1996
Person Types
- Staff
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Collaborations and top research areas from the last five years
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Development of phosphinic acid-based prodrugs towards MMPs inhibition in tumor progression and metastasis
1/09/24 → 30/08/27
Project: Internal Research Project
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Suzhou Industrial Park High Quality Innovation Platform of Functional Molecular Materials and Devices
Yang, L., Liu, C., Lu, Q., Papadikis, K., Choi, H., Lin, Y., Xue, X., Huang, X., Ding, M., Wang, X., Zhang, Q., JIN, X., Matziari, M., Ding, L., Li, D., Dennis, J., Dong, Q., 张开周, 由冬琦 & 郜明文
1/09/23 → 30/08/25
Project: Governmental Research Project
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Development of phosphinic acid-based prodrugs towards MMPs inhibition in tumor progression and metastasis
Project: Internal Research Project
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Dual HepC hepacivirin and HIV-1 proteases phosphorus-based inhibitors
1/09/21 → 31/08/24
Project: Internal Research Project
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Dual HepC hepacivirin and HIV-1 proteases phosphorus-based inhibitors
Matziari, M., Amigues, E., Lin, Y., O’Connor, D., O, P., Pushpakom, S., Ruiz-Carrillo, D. & Kellow, R.
1/01/20 → 31/12/22
Project: Internal Research Project
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Development of phosphinic HIV-1 protease inhibitors potential prodrugs
Matziari, M., 2024, 24th Tetrahedron Symposium.Research output: Chapter in Book or Report/Conference proceeding › Conference Proceeding › peer-review
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GLP-1 Receptor Signaling Has Different Effects on the Perikarya and Axons of the Hypophysiotropic Thyrotropin-Releasing Hormone Synthesizing Neurons in Male Mice
Ruska, Y., Peterfi, Z., Szilvásy-Szabó, A., Ková ri, D., Hrabovszky, E., Doroghá zi, B., Gereben, B., Tó th, B., Matziari, M., Wittmann, G. & Fekete, C., 1 Feb 2024, In: Thyroid. 34, 2, p. 252-260 9 p.Research output: Contribution to journal › Article › peer-review
3 Citations (Scopus) -
Phosphorus-based enzyme inhibitors and prodrugs
Matziari, M., 2024, RSC International Accreditation Research webinar series.Research output: Chapter in Book or Report/Conference proceeding › Conference Proceeding › peer-review
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Symmetrical phosphinic acids: Synthesis and esterification optimization toward potential HIV prodrugs
Matziari, M., Hayat, K., Zhang, Q. & Nixon, G., 2024, In: ACS Omega.Research output: Contribution to journal › Article › peer-review
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Diastereoselective synthesis of a novel phosphinic peptide as ACE inhibitor: Fragment-based design approach
Abdou, M. M., Dong, D., O'Neill, P. M., Amigues, E. & Matziari, M., Feb 2023, In: Arabian Journal of Chemistry. 16, 2, 104499.Research output: Contribution to journal › Article › peer-review
Open Access1 Citation (Scopus)
Activities
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Development of phosphinic acid-based prodrugs towards MMPs inhibition in tumor progression and metastasis
Magdalini Matziari (Supervisor)
Sept 2024Activity: Supervision › PhD Supervision
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SURF-2024-0283, “Optimization of nitroolefins synthesis from amino acids”
Magdalini Matziari (Supervisor)
29 Aug 2024Activity: Supervision › Completed SURF Project
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Structure-Activity Relationship Studies of viral protease inhibitors
Magdalini Matziari (Supervisor)
Mar 2024Activity: Supervision › PhD Supervision
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Nitroolefins synthesis optimization
Magdalini Matziari (Supervisor)
2024Activity: Supervision › Completed SURF Project
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Phosphinate prodrugs based on flavonoids and carbohydrates
Magdalini Matziari (Speaker)
27 Sept 2023Activity: Talk or presentation › Invited talk