Aims of the course:
The course is an expansion and in depth analysis of the required course (code number: ΝΠ-38) of the same semester and its aim is the application of modern aspects of medicinal chemistry in drug design and in the successful confrontation of pathologic conditions using contemporary approaches of medicinal chemistry & chemical biology. Specifically:
- Scaffolds and physicochemical properties of drug-like molecules. Principles of identification, optimization and production of new chemical entities.
- Oxidative stress, antioxidant pharmacotherapy. Oxidative stress and biologic stress in pathologic conditions. Pharmacochemical aspects of biological stress, relations between biological and oxidative stress. Indices of oxidative and biologic stress and their interrelationships. Consequences of oxidative and of biologic stress on health.
By the end of this course, the students will have a working knowledge of:
- The three dimensional graphical depiction of compounds using a molecular modeling software.
- The structural energy minimization implementing molecular & quantum mechanism.
- The two dimensional drawing of compounds and the calculation of distribution & partition coefficients.
- The involvement of oxidative stress in pathologic conditions and diseases and the response of the organism to xenobiotics
- The physiologic defensive mechanisms as stress response
Course Content (Syllabus)
1) Vassilis Demopoulos
Chemical biology in medicinal chemistry, with focus on:
a) stereo-chemical factors and biological activity (optical isomerism, spatial isomerism, conformational space)
b) physical & chemical properties important in biological activity (lipophilicity, hydrophobicity, ionization, solubility, molecular polar surface area)
d) thermodynamic analysis of ligand-receptor interactions
e) permeability through biological membranes
2) Eleni Rekka
In this course, pharmacochemical aspects of oxidative and biologic stress, their indices and their relationships are analysed. Importance of oxidative and of biologic stress in diseases of the modern society, e.g. Alzheimer’s and Parkinson’s diseases, development of biologic stress and other pathologic conditions is examined. Xenobiotic toxicity connected to free radical formation, toxic metabolites, antioxidant intervention are presented.
3) Ioannis Nicolaou
Pharmacochemical approach for the management of the lack of selectivity toward tumor cells and low therapeutic index of the antineoplastic agents, via two primary strategies:
a) through the design of targeted anticancer prodrugs for tumor site-specific activation, and
b) through a tumor-targeting drug delivery system which consists of a tumor recognition moiety (as monoclonal antibodies, polyunsaturated fatty acids, folic acid, hyaluronic acid, and oligopeptides) and a cytotoxic warhead connected directly or through a suitable linker to form a conjugate.
Additional bibliography for study
1) Βασίλης Δημόπουλος
- Richard B. Silverman “The Organic Chemistry of Drug Design and Drug Action”, Academic Press, 2004, ISBN-10: 0126437327
-Joseph J. Cannon “Pharmacology for Chemists”, Oxford University Press, 2007, ISBN-10: 0841239274
- Jonathan M. Goodman “Chemical Applications of Molecular Modelling”, The Royal Society of Chemistry, 1998, ISBN: 0854045791
- M. P. Edwards and D. A. Price, "Role of Physicochemical Properties and Ligand Lipophilicity Efficiency in Addressing Drug Safety Risks". Ann. Rep. Med. Chem., 45: 381–391 (2010)
- A. Avdeef, “Physicochemical profiling (solubility, permeability and charge state)”, Curr. Top. Med. Chem., 1, 277-351 (2001)
- N. A. Meanwell “Synopsis of Some Recent Tactical Application of Bioisosteres in Drug Design”, J. Med. Chem., 54, 2529–2591 (2011)
- J. Clayden, S. R. LaPlante et. al. “The Challenge of Atropisomerism in Drug Discovery” Angew. Chem. Int. Ed., 48, 6398 – 6401 (2009)
2) Ελένη Ρέκκα
- Ε.Α. Ρέκκα, Π.Ν. Κουρουνάκης, «Οργανική Φαρμακευτική Χημεία: Θέματα Φαρμακοχημείας-Σχεδιασμού Φαρμάκων», Εκδ. Φ. Χατζηπάντου, 2010 (ISBN 978-960-98594-3-1)
- R. Rodrigo, “Oxidative Stress and Antioxidants: Their Role in Human Disease”, 2009, Nova Science Pub Inc.
3) Ιωάννης Νικολάου
- Journal of Medicinal Chemistry (ACS Publications)
- Bioorganic & Medicinal Chemistry Letters - Elsevier
- Bioorganic & Medicinal Chemistry (ISSN 0968-0896)