MEDICINAL AND TOXICOLOGICAL CHEMISTRY 2

Single discipline educational activity

Course Sheet

Course code:

00204

Academic Year of enrolment:

2022

Year of supply:

2025/2026

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:

CACCIATORE Ivana

Cycle:

Second semester

Obligatory attendance:

Yes

Minimum hours of attendance:

Hours of classroom activity:

Individual study hours:

161

Prerequisites:

Students attending the Pharmaceutical and Toxicological Chemistry II course must have a good familiarity with organic compounds and the basic mechanisms of organic chemistry, as well as basic notions of physiology and pharmacology.

Objectives

The course provides students with the tools for an analytical and critical approach to the discipline. Particular space is dedicated to understanding the phases of drug design and the molecular optimization approaches of the parent drugs. In the second part of the course, selected topics of pharmaceutical chemistry are proposed (antimicrobials, antiparasitics, anticancer drugs, hormones, cardiovascular drugs), the treatment of which insists on mechanistic, design and synthetic aspects. Students are provided with information on the chemical and chemical-physical properties of drugs, on their biological effects, on the molecular-based mechanism of action, on the relationships between structure and biological activity, on pharmacokinetic properties, on metabolic and toxicological pathways. The subject is characterized in its increasingly interdisciplinary connotations, with the aim of raising student awareness of the fascinating world of medicine.
Classroom learning: students are interactively stimulated to apply the knowledge they acquire through regular attendance to:
- understanding the relationships between chemical structure, properties, reactivity and biological activity of a drug
- prediction of the pharmacokinetic behavior and metabolic fate of bioactive molecules
- structural and mechanistic characterization of molecular targets
- formulation of drug modification strategies
- understanding of synthesis methodologies
- acquisition of correct terminology
Expected results: the student is expected to learn the fundamentals of the action of drugs and their complex interaction with different biological systems on a stereo-electronic basis. The methodological approach to which he has been directed will allow him to independently develop concepts and strategies, illustrated in class with specific examples, in any area of the discipline. The student will be able to acquire the ability to develop the rational design and synthetic strategy of drugs for new macromolecules identified as targets. The preparation gained enables students to undertake a period of internship in a Pharmaceutical Chemistry laboratory.

Contents

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

Extended Syllabus

1. INTRODUCTION TO PHARMACEUTICAL CHEMISTRY

The targets of drugs: proteins, nucleic acids, lipids, and carbohydrates.

2. ANTI-INFECTIVE AND ANTI-PARASITIC DRUGS

Introduction to anti-infective drugs. Classification. Mechanisms of resistance to anti-infective agents. Antibiotic resistance. Main mechanisms of action of anti-infective drugs.

DISINFECTANTS AND ANTISEPTICS
Definition and classification.
Oxidizing substances: chlorine, hypochlorite, iodine, povidone-iodine, hydrogen peroxide.
Reducing substances: silver sulfadiazine.
Organic substances: ethyl alcohol, phenols and derivatives, quaternary ammonium salts, biguanides.

ANTIBIOTICS
Antibiotics that interfere with the biosynthesis of the bacterial wall (peptidoglycan): physicochemical properties, structure of the peptidoglycan:
a) β-lactam antibiotics: mechanism of action, mechanisms of resistance. 6-APA, first penicillins, nomenclature, stability in acid and basic environments, stability to beta-lactamases, structure-activity relationships of penicillins. Natural penicillins, acid-fast penicillins for oral administration, beta-lactamase-resistant penicillins, and carboxypenicillins. Penicillins: adverse reactions.
Cephalosporins: nomenclature, stability in acid and basic environments. I, II, III, IV and V generation cephalosporins. Structure-activity relationships of cephalosporins. Monobattami. Beta-lactamase inhibitors. Penicillin and beta-lactamase inhibitor combinations. carbapenems.
b) Phosphomycin
c) Glycopeptides: vancomycin and teicoplanin.
Antibiotics that interfere with protein synthesis:
a) Macrolides: erythromycin, clarithromycin, and azithromycin
b) Lincosamides
c) Amphenicols: chloramphenicol
d) Tetracyclines: nomenclature and chemical-physical properties. Stability in acid and basic environment. Structure-activity relationships of tetracyclines. Natural, semi-synthetic and synthetic tetracyclines. Mechanism of action of tetracyclines.
e) Aminoglycosides

ANTIBACTERIAL CHEMOTHERAPY
Sulfonamides: mechanism of action, structure-activity relationships, therapeutic applications.
Trimethoprim.
Nitroheteroaromatic compounds: Metronidazole.
Quinolones: mechanism of action, structure-activity relationships, therapeutic applications.
Oxazolidinones: mechanism of action, structure-activity relationships, therapeutic applications

ANTIMYCOBACTERIAL CHEMOTHERAPY
Drugs for the treatment of tuberculosis. Mechanism of action. Isoniazid, pyrazinamide, rifamycins, ethambutol, streptomycin, fluoroquinolones, p-aminosalicylic acid, cycloserine, delanamib, and pretomanid.
Drugs for the treatment of leprosy. Rifampicin, Clofazimine, Dapsone.

ANTIPROTOAZOAR CHEMOTHERAPIC
Drugs for the treatment of malaria. Quinine, arylaminoalcohols, 4-aminoquinolines, 8-aminoquinolines, artemisinins, folic acid inhibitors. Drugs for the treatment of trypanosomiasis, leishmaniasis, amoebiasis, giardiasis, trichomoniasis, and toxoplasmosis.

ANTIFUNGAL CHEMOTHERAPY
Classification of antifungal drugs. Polyenes, Azoles, Benzofuran-cyclohexenes, Pyrimidines.

ANTIVIRAL CHEMOTHERAPY
Drugs that interfere with the penetration of the virus into the host cell: amantadine, rimantadine, interferons, and neuraminidase inhibitors.
Viral replication inhibitors: nucleoside analogues.
Antiretroviral agents for HIV and AIDS: Nucleoside and non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, entry and fusion inhibitors.
Antiviral agents for hepatitis C.

3. ANTICANCER DRUGS

Alkylating anticancer drugs. Nitrous mustards, aziridine drugs, alkyl sulphonate drugs, nitrosureas, organoplatinum complexes, folic acid analogues, pyrimidine base analogues, purine base analogues. DNA intercalating drugs, non-DNA intercalating drugs, drugs that affect the tubulin/microtubule system, tubulin polymerization inhibitors, microtubule depolymerization inhibitors, and protein kinase inhibitors.

4. DRUGS FOR THE ENDOCRINE AND METABOLIC SYSTEMS

Non-steroidal anti-inflammatory drugs: mechanism of action. Salicylic derivatives. Derivatives of aniline. Enolic acids. Aryl- and heteroaryl-alkanoic acids. Arylacetic derivatives. Coxibs.

Insulin and hypoglycemic drugs. Insulin. Modified insulins. Oral hypoglycaemics. Drugs that interact with the incretin system. DPP-IV inhibitors. SGLT2 transporter inhibitors.

Thyroid drugs. T3 and T4 hormones. Thioamides.

Steroid hormones. Estrogens and natural and synthetic derivatives. Antiestrogens: prevented estrogenic derivatives, triphenylethylene antiestrogens, aromatase inhibitors. Progestogens. Progesterone antagonists. Natural and synthetic androgens. Antiandrogens. Adrenal cortex hormones. Glucocorticoids and mineralocorticoids.

Drug Structures To Know:

PENICILLINS:6-APA, PENICILLIN G AND V, AMPICILLIN, BACAMPICILLIN, METHICILLIN, OXA-, CLOXA- AND DICLOXACILLIN, CARBENICILLIN, TICARCILLIN, PIPERACILLIN
Cephalosporins: 7-ACA, Cephalosporin C, Cephalexin and Cephazoline, Cefaclor, Cefuroxime, Ceftriaxone, Cefepime
MONOBACTAM: AZTREONAM
BETA-LACTAMASE INHIBITORS: CLAVULANIC ACID, SULBACTAM
CARBAPENEMS: THIENAMYCIN, IMIPENEM
PHOSPHOMYCIN
VANCOMYCIN AND TEICOPLANIN (KNOWING TO RECOGNIZE THE STRUCTURE)
ERYTHROMYCIN, CLARITHROMYCIN, AZITHROMYCIN (KNOWING TO RECOGNIZE THE STRUCTURE)
CHLORAMPHENICOL
TETRACYCLINE: CHLORTETRACYCLINE, TIGECYCLINE
AMINOGLYCOSIDE ANTIBIOTICS: GENTAMICIN, TOBRAMYCIN, STREPTOMYCIN
ANTIBACTERIAL CHEMOTHERAPY: SULFANILAMIDE, SULFAMETOXAZOLE, SULFASALAZINE, TRIMETHOPRIM, NITROFURANTOIN, METRONIDAZOLE, NORFLOXACIN, CIPROFLOXACIN, LINEZOLID.
ANTIMYCOBACTERIAL CHEMOTHERAPY: ISONIAZID, PYRAZINAMIDE, RIFAMYCINS (KNOWING TO RECOGNIZE THE STRUCTURE OF RIFAMPICIN, RIFAPENTINE, RIFABUTIN, RIFALAZIL), ETAMBUTOL, OFLOXACIN, GATIXIFLOXACIN, CILOSERINE, PRETOMANID, DAPSONE
ANTIPROTOAZOAR CHEMOTHERAPY: QUININE, MEFLOQUINE, CHLOROQUIN, PRIMAQUIN, ARTEMISININ, SULFADOXINE, PYRIMETHAMINE, ATOVAQUONE, PROGUANIL, METRONIDAZOLE
ANTIFUNGAL CHEMOTHERAPIC: AMPHOTERICIN B AND NISTATIN (knowing how to recognize the structure), ECONAZOLE, MICONAZOLE, FLUCONAZOLE, GRISEOFULVIN, FLUCITOSIN
ANTIVIRAL CHEMOTHERAPY: AMANTADINE, RIMANTADINE, ZANAMIVIR, ACICLOVIR, VALACICLOVIR, GANCICLOVIR, VALGANCICLOVIR, AZT, LAMIVUDINE, NEVIPARINA, SAQUINAVIR, RITONAVIR, ELVOTEGRAVIR, SOFOSBUVIR
ANTICANCER DRUGS: MECHLORETHAMINE, CHLORAMBUCYL, CYCLOPHOSPHAMIDE, IFOSFAMIDE, MITOMYCIN, CARMUSTINE, LOMUSTINE, CISPLATINUM, OXALIPLATINUM, METHOTRESXATE, 5-FLUOROURACIL, CYTARABINE, PENTOSTATIN, DACTINOMYCIN, BLEOMYCINS (KNOWING TO RECOGNIZE THE STRUCTURE), DOXORUBICIN, VALRUBICIN, PODOPHILLOTOXIN, CAMPOTHECIN, TOPOTECAN, VINCRISTINE, VINBLASTINE, PACLITAXEL, DOCETAXEL (KNOWING TO RECOGNIZE THE STRUCTURE), IMATINIB.
ANTI-INFLAMMATORY DRUGS: SALICYLIC ACID, MESALAZINE, PARACETAMOL, PYROSXICAM, IBUPROFEN, DICLOFENAC, LUMIRACOXIB, CELECOXIB, VALDECOXIB.
STEROID HORMONES: ESTRADIOL, 17-α-ETHYNYL ESTRADIOL, TAMOXIFEN, PROGESTERONE, NORGESTREL, MIFEPRISTONE, TESTOSTERONE, OXANDROLONE, NANDROLONE, ALDOSTERONE, CORTISOL, DEXAMETHAONE, BETAMETHASONE
HYPOGLYCEMIC DRUGS: CARBUTAMIDE, TOLBUTAMIDE, ROSIGLITAZONE, LIRAGLUTIDE, ANAGLIPTIN
THYROID DRUGS: T3 AND T4, METHYMAZOLE, CARBIMAZOLE, AMIODARONE

Synthesis of drugs to know:

PEROXIDE, ETHANOL, 6-APA, METHICILLINE, TICARCILLIN, 7-ACA, CEFUROXIME, SULPHAMIDICS (GENERAL METHOD), NITROFURANS (GENERAL METHOD), NORFLOXACIN, LINEZOLID, ISONIAZIDE, PYRAZINAMIDE, DAPSONE, METRONIDAZOLE, ECONAZOLE, MCONAZOLE, FLUCONAZOLE, AZT, CHLORAMBUCYL, CYCLOPHOSPHAMIDE, IMATINIB (DESIGN), ACETYLSALICYLIC ACID, PARACETAMOL, PYROSXICAM, IBUPROFEN.

Recommended Bibliography

The following reference texts are recommended:
1. Patrick G.L.: Pharmaceutical Chemistry (III integrated Italian edition, edited by Costantino, G., based on the V American edition of An introduction to Medicinal Chemistry), Edises Srl, Naples (2015)
2. Various authors: Pharmaceutical Chemistry (2nd Edition), edited by Gasco, A., Gualtieri, F., Melchiorre, C., Casa Editrice Ambrosiana, Rozzano (MI) (2020)

The slides shown in lessons in the current academic year are available in PDF version on the e-learning platform.

Methods of Provision

Conventional

Teaching Methods

Lectures and classroom exercises. Classroom exercises consist of presentations by the student on the design, synthesis and biological activity of new molecules under development starting from the drug classes discussed in class. To prepare the presentation, the student is expected to carry out bibliographic research on scientific databases, such as Scopus and Pubmed. Team working activities are also planned for students who choose very broad topics for discussion.

Evaluation methods

Verification of learning:

During the course of the lessons, 3 ongoing written tests and an interactive oral didactic test are scheduled (power point presentation on drug classes under development).
For students who do not participate in the ongoing tests, the learning assessment includes a written test and an oral exam.
Written test lasting 2 hours with 10 questions. Minimum score for admission to the oral test: 18/30.
Oral test consists of an in-depth interview on various topics covered in class.

Contacts/More Information

Mandatory attendance.

Università degli Studi
"G. d'Annunzio"

Chieti - Pescara

Aree