MEDICINAL AND TOXICOLOGICAL CHEMISTRY 2

Università degli Studi
"G. d'Annunzio"

Chieti - Pescara

Single discipline educational activity

Course Sheet

Course code:

00204

Academic Year of enrolment:

2018

Year of supply:

2021/2022

Type of Course:

Characterising

Degree:

Course of Single Cycle Degree 5 years in MEDICINAL CHEMISTRY AND PHARMACEUTICAL TECHNOLOGY

Disciplinary Sector:

Pharmaceutical Chemistry

Language:

Italian

Location:

CHIETI

Credits:

Programme Year:

Professor and Collaborators:

LUISI Grazia

Cycle:

Second semester

Obligatory attendance:

Yes

Minimum hours of attendance:

Hours of classroom activity:

Individual study hours:

162

Prerequisites:

Medicinal and Toxicological Chemistry I

Organic Chemistry II

Objectives

This part of the course emphasizes the interdisciplinary aspects of Medicinal Chemistry, with the aim of sensitizing students to the exciting world of drugs through the acquisition of a scientific and critical approach to the discipline. Particular attention is devoted to the illustration of drug design fundamentals and to the comprehension of molecular mechanisms underlying biological action of pharmaceuticals. The selected drug classes (antibacterials, antivirals, antifungals, antineoplastic drugs, hormones, diuretics) presented in the systematic part of the course are treated under a variegated perspective, at the interface between chemistry and biology.

Contents

INTRODUCTION TO DRUG DESIGN-DISINFECTANTS AND ANTISEPTICS-ANTIMICROBIALS-ANTIPARASITAL AGENTS-ANTICANCER DRUGS-STEROID HORMONES-AUTACOIDS AND NON STEROIDAL ANTIINFALMMATORY DRUGS-PEPTIDE HORMONES-CARDIOVASCULAR AGENTS-DESIGN AND SYNTHESIS OF SIGNIFICANT DRUGS.

Extended Syllabus

1) INTRODUCTION
Principles of drug discovery, design, and development. Pro-drug and bio-precursor design. Pro-Tide drugs. Therapeutic targets: enzymes, receptors, cellular structures.

2) DISINFECTANTS AND ANTISEPTICS
Alcohols and related compounds; phenols and derivatives; oxidizing agents; halogen- containing compounds; cationic surfactants; dyes; mercurials.

3) ANTIMICROBIALS
Antibacterials: sulfonamides and dihydrofolate reductase inhibitors; beta-lactam antibiotics; macrolide antibiotics; lincomycins; tetracyclines; chloramphenicol and analogs; aminoglycoside antibiotics; glycopeptide antibiotics, polypeptide antibiotics; antimicrobial cationic peptides and analogs, fosfomycin; other antibacterial agents: nitrofurans, metronidazole, methenamine, quinolones, oxazolidiones. Antimycobacterials: first- and second-line antitubercolar drugs, novel agents targeting the cell wall biosynthesis, bedaquiline; antileprotic drugs.

4) ANTIPARASITAL DRUGS
Antiprotozoal agents: antimalarials; chemotherapy of toxoplasmosis, amebiasis, giardiasis, trichomoniasis, trypanosomiasis, leishmaniasis, pneumocystosis. Anthelmintics. Antiviral drugs: treatment of HIV, HCV, and HSV infections; anti-influenza agents; tretment of CoViD19. Antifungals: allylamines; griseofulvin; azole compounds; miscellaneous antifungal agents; polyene macrolides; echinochandins.

5) ANTICANCER DRUGS
Alkylating agents; metalating compounds; antimetabolites; Vinca alkaloids, hemiasterlins and analogs (mentions), taxoids and other natural products; actinomycins; anthracyclines; bleomycins; mitomycins; asparaginase. Enzymatic inhibitors of tyrosin kinases and (mentions) histone deacetylases, matrix metalloproteinases, carbonic anhydrases.

6) STEROID HORMONES
Structure, nomenclature, and biosynthesis of steroid hormones; adrenal cortex hormones: glucocorticoids and mineralocorticoids; mineralocorticoid antagonists. Sex hormones: estrogens; antiestrogens; progestins; oral contraceptives; antiprogestins; androgens; antiandrogens; anabolic agents.

7) AUTACOIDS AND NON STEROIDAL ANTI-INFLAMMATORY DRUGS
Eicosanoids: biosynthesis, structure, and biological properties of prostaglandins, prostacyclin, tromboxanes and leukotrienes. Non steroidal anti-inflammatory drugs: salicylates and mefenates; aryl- and heteroaryl-acetic acid derivatives, aryl-propionic acid derivatives; oxicams; pyrazolidine derivatives; acetanilids; COX2 selective inhibitors. Treatment of asthma.

8) PEPTIDE HORMONES
Hormones of the hypothalamus-hypophysis axis and synthetic analogues; hormones of the thyroid gland; uterotonic and tocolytic agents. Pancreatic hormones and drugs acting on glucidic metabolism.

9) CARDIOVASCULAR DRUGS
Antithrombotic agents: anticoagulant, antiplatelet, and fibrinolityc drugs. The renin-angiotensin system: renin inhibitors, ACE inibitors, AT1-antagonists.

10) SYNTHESIS OF SIGNIFICANT DRUGS
Sulfamethoxazole; sulfafurazole; sulfamethizole; trimetoprim; methicillin; azidocillin; bacampicillin; flucloxacillin; ticarcillin; cefaclor; cefoperazone; ceftriaxone; cefpodoxime proxetil; clindamycin; doxycycline; lymecycline; chloramphenicol; amikacin; netilmicin; linezolid; nalidixic acid; norfloxacin; oxolinic acid; rifampin; dapsone; metronidazole; nitrofurantoin; cloroquine; primaquine; oxamniquine; azidothymidine; nevirapine; ribavirin; butenafine; butoconazole; ketoconazole; chlorambucil; cyclophosphamide; busulfan; carmustine; lomustine; estramustine; methotrexate; cytarabine; fluorouracil; pregnenolone; methylprednisolone; trilostane; spironolactone; ethynodiol diacetate; levonorgestrel; tolmetin; indomethacin; ibuprofen; diclofenac; celecoxib; captopril; enalapril; quinapril; warfarin; melagatran.

11) SELECTED EXAMPLES OF DRUG DESIGN
Pro-Tide pro-drugs; activation of bio-precursors by reductive or oxidative pathways; omapatrilat; pro-drugs of penicillins and cephalosporins; phenylglycil-boronic acids as beta-lactamase inhibitors; cephalosporin-quinolone conjugates; siderophore- cephalosporin conjugates; oxamniquine; ritonavir; cyclophosphamide; glutathione- nitrogen mustard conjugates; estramustine phosphate; sulindac.

Recommended Bibliography

1. Patrick G.L.: Chimica Farmaceutica (III Italian Edition, edited by Costantino, G., based on the V American Edition of An introduction to Medicinal Chemistry), Edises Srl, Napoli (2015)
2. Authors : Chimica Farmaceutica (II Edizione), edited by Gasco, A., Gualtieri, F., Melchiorre, C., Casa Editrice Ambrosiana, Rozzano (MI) (2020)
3. Authors: Principi di Chimica Farmaceutica (VI Italian Edition, edited by Dall’Acqua, F., based on the VII American Edition of Foye’s Principles of Medicinal Chemistry,edited by Lemke T. L. and Williams D. A.), Piccin Nuova Libraria, Padova (2014)
4. Authors: Chimica Farmaceutica (I Italian Edition, translation of the XII American Edition of Wilson & Gisvold’s Textbook of Organic, Medicinal and Pharmaceutical Chemistry, edited by Beale, J. M., jr. and Block, J. H.) Casa Editrice Ambrosiana, Rozzano (MI) (2014)

Methods of Provision

Conventional

Teaching Methods

Traditional teacher-led lessons

Evaluation methods

Verification of learning:

The examination is made up of a 2 hour written test and a subsequent oral part

The minimum score to be admitted to oral examination is 18/30.

Contacts/More Information

The frequence to the course is mandatory.

Università degli Studi
"G. d'Annunzio"

Chieti - Pescara

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