00126 - Medicinal and Toxicological Chemistry I;

Academic Year 2021/2022

Learning outcomes

At the end of the course the student knows: - the basic concepts of general medicinal and toxicological 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 ofdrugs. Interaction between a drug and a molecular target: bonds involved in the interaction. Stereochemistry and drug action: optical, geometrical andconformational isomerism. Pharmacokinetic phase: absorption, distribution, elimination; metabolism: phase I and phase II reactions. Introduction to drug design.

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 the eicosanoids system: nimesulide, coxibs; salycilic and anthranylicacid derivatives; acetic and propionic acid derivatives; pyrazolidindiones; benzothiazines; pyrazolinones; acetanilides.
Drugs acting on the steroid hormones system: estrogens; androgens; progestins; glucocorticoids; mineralocorticoids.

Readings/Bibliography

A. GASCO, F. GUALTIERI, C. MELCHIORRE Chimica Farmaceutica
Casa Editrice Ambrosiana, Milano, 2015

G.L. PATRICK Introduzione alla Chimica Farmaceutica. Seconda Edizione
EdiSES, Napoli, 2010 (ed. originale 2009)

G. GRECO Farmacocinetica e Farmacodinamica su Basi Chimico-Fisiche
Loghìa, Napoli, 2007

D.A. WILLIAMS, T.L. LEMKE (Eds.) Foye's Principles of Medicinal Chemistry. Fifth Edition
Lippincott Williams & Wilkins, Philadelphia, 2002
(Ed. italiana, Piccin, Padova, 2005)

M.E. WOLFF (Ed.) Burger's Medicinal Chemistry and Drug Discovery. Fifth Edition
John Wiley & Sons, New York, 1995

C. HANSCH (Ed.) Comprehensive Medicinal Chemistry
Pergamon Press, Oxford, 1990

D. LEDNICER, L.A. MITSCHER The Organic Chemistry of Drug Synthesis, voll. 1-6
John Wiley & Sons, New York, 1977, 1980, 1984, 1990, 1995, 1999

R.B. SILVERMAN The Organic Chemistry of Drug Design and Drug Action
Academic Press, San Diego, 1992

F. GUALTIERI (Ed.) New Trends in Synthetic Medicinal Chemistry
Wiley-VCH, Weinheim, 2000

C.G. WERMUTH (Ed.) Le applicazioni della Chimica Farmaceutica
EdiSES, Napoli, 2000 (ed. originale 1996)

Office hours

See the website of Maurizio Recanatini