00126 - Medicinal and Toxicological Chemistry I;

Learning outcomes

At the end of the course the student knows: - the basic concepts of general medicinal chemistry concerning drug-target molecular interactions, pharmacokinetics and drug discovery; - the fundamental aspects concerning the design, the synthesis, the mechanisms of action at the molecular level and the structure-activity relationships of some classes of drugs attributable to anti-infectious and anticancer chemotherapeutics, anti-inflammatories and drugs active on the hormonal systems of steroids. In addition, the student: - is able to understand the mechanisms of action of enzyme inhibitors and steroid drugs based on the chemical characteristics of the molecules involved and knows how to analyze their structure-activity relationships; - is able to critically evaluate synthetic strategies for the preparation of new drugs belonging to these classes; - has the ability to critically bring together medicinal chemistry texts and articles on the subject.

Course contents

GENERAL PART
Definition of medicinal chemistry. Process of action of drugs. Molecular targets of drugs. Interaction between a drug and a molecular target: bonds involved in the interaction. Stereochemistry and drug action: optical, geometrical and conformational isomerism. Pharmacokinetic phase: absorption, distribution, elimination; metabolism: phase I and phase II reactions.

DESCRIPTIVE PART
Drugs acting on the biosynthesis of the cell wall: beta-lactam antibiotics; peptide antibiotics; isoniazide, ethambutol.
Drugs acting on the function and biosynthesis of components of the cell membrane: peptide antibiotics; macrolide-polyene antibiotics; azoles, allylamines.
Drugs acting on the protein biosynthesis: tetracyclines; aminoglycosides; macrolide antibiotics; ansamycins.
Drugs acting on the DNA biosynthesis: sulfonamides; diamino-pyrimidines, -triazines and analogues; purines, pyrimidines and analogues.
Drugs acting on DNA: nitrogen mustards, nitrosoureas, ethyleneimines, mitomycins, platinum derivatives; pentamidine, distamycin and analogues; actinomycins, quinolines, acridines; anthracyclines and derivatives; quinolones.
Drugs acting on mitosis: Vinca alkaloids; taxol derivatives.
Drugs acting on intracellular signaling: kinase inhibitors.
Drugs acting on the eicosanoids system: nimesulide, coxibs; salycilic and anthranylic acid derivatives; acetic and propionic acid derivatives; pyrazolidindiones; benzothiazines; pyrazolinones; acetanilides.
Drugs acting on the steroid hormones system: estrogens; androgens; progestins; glucocorticoids; mineralocorticoids.

INTRODUCTION TO COMPUTATIONAL DRUG DESIGN
Methods based on 3D models of molecules (ligand-based and target-based approaches; virtual screening). Data-based methods (QSAR, machine learning, network-based).

Readings/Bibliography

For further readings, please refer to:

A. GASCO, F. GUALTIERI, C. MELCHIORRE, Chimica Farmaceutica, CEA, Milano, 2019

G.L. PATRICK, Chimica Farmaceutica, III Edizione italiana, EdiSES, Napoli, 2015.

D.A. WILLIAMS, T.L. LEMKE, Foye's Principi di Chimica Farmaceutica, VI Edizione italiana, Piccin, Padova, 2014.

Teaching methods

Lectures

Assessment methods

The learning verification test is oral. It aims to evaluate the level of knowledge, a) of the basic concepts of medicinal chemistry and, b) of the fundamental aspects concerning the design, synthesis, mechanisms of action at the molecular level and structure-activity relationships of the drug classes illustrated during the course.
As a preliminary test, the student will be asked to discuss the syntheses of two drugs among those listed in the program. If this test is passed, the exam will continue with an interview on the other course  topics.

Teaching tools

The teaching material (slides) presented during classes is available on the Virtuale platform.

Office hours

See the website of Maria Laura Bolognesi