COMPOSTI NATURALI PER L'INDUSTRIA FARMACEUTICA E AGROALIMENTARE

The course aims to provide students with essential knowledge on the biosynthesis, properties, biological and applied relevance of bioactive natural compounds, including some examples of industrial synthesis. Basic knowledge will also be provided on the interaction of natural compounds with receptors and enzymes, on xenobiotic metabolism, and on the role of nutraceuticals in nutrition. Detailed information will be provided on the most modern extraction and purification techniques with particular attention to low environmental impact techniques. Laboratory activities will be dedicated to the extraction and purification of one or more natural compounds from readily available plant products.

At the end of the course, students must acquire reasoning skills and independent judgment on the specific topics of the course, and be able to discuss each topic with scientific method and appropriate language.

Furthermore, in reference to the so-called Dublin Descriptors, this course contributes to acquiring the following competencies:

D1 - Knowledge and understanding: At the end of the course, students will acquire knowledge regarding the main classes of natural compounds and their possible applications in the pharmaceutical and agri-food sectors. At the end of the course, students will be able to rationalize the structure-property correlations of natural compounds and their synthetic analogues using inductive and deductive reasoning.

D2 - Applying knowledge and understanding:

Students will acquire the scientific method to study and understand the chemical properties of natural compounds and synthetic analogues in relation to their structure. Students will be able to use the acquired competencies to utilize natural compounds or their synthetic analogues for future professional needs and for research in the pharmaceutical, nutritional, and agri-food sectors. Students will be able to solve chemical problems inherent to the chemistry of natural compounds and will be able to develop scientific projects related to the course themes.

D3 - Making judgments: At the conclusion of the course, students will develop independent judgment useful for adapting the acquired knowledge to different work contexts and diverse themes. Students will be able to find information on structures, properties, sources, and uses of natural compounds through open access databases, scientific literature, etc.

At the end of the course, students will be able to formulate reflections on important ethical or scientific issues related to the use of compounds of natural origin (safety, environmental sustainability, economic impact, etc.).

Regarding laboratory activities, at the end of the course students will be able to design experimental activities evaluating their timing and methods, independently judge the results obtained and quantify them. During laboratory activities, they must also demonstrate the ability to work in groups.

D4 - Communication skills: At the end of the course, students will be able to communicate with proper language skills (in Italian and English) and with terminological rigor, regarding the chemistry of natural compounds and their applications, illustrating their motivations and results.

During laboratory experiences, they will have to interact with colleagues, plan and manage the time necessary to carry out the laboratory experience, work both in groups and independently, adapting to the different laboratory experiences proposed by the instructor.

At the end of the course, students will be able to transmit the acquired knowledge to undergraduate students in both theoretical and experimental contexts.

D5 - Learning skills:

At the end of the course, students must be able to:

a) Identify and effectively consult scientific literature, specialized databases, and online resources to obtain information on natural compounds, structures, biological activities, and applications.

b) Independently acquire knowledge and data on natural compounds, exploring experimental techniques (such as extraction, purification) and new approaches to address emerging scientific challenges. This also includes autonomy in understanding issues related to sustainability, safety, and ecological impacts, which are crucial in professional and applied research contexts.

c) Address complex scientific issues that require an integrated approach between chemistry, biology, ecology, pharmacology, and environmental sciences.

d) Be able to collect and interpret scientific data to justify and defend in a clear and convincing manner the scientific, social, and economic importance of natural compounds in both specialized contexts (e.g., pharmacological research) and broader ones (regulation, marketing, or education).

Information for students with disabilities and/or specific learning disorders (SLD):

To ensure equal opportunities and in compliance with current laws, students concerned are invited to request a personal meeting in order to plan any necessary compensatory and/or dispensatory measures, based on the educational objectives and their specific needs.

English-Friendly Course Format

This course is offered in an English-Friendly format. The lessons will be primarily conducted in Italian, but international mobility students will receive comprehensive support through English-language teaching materials. Students enrolled in international mobility programs may request to take examinations in English. The English-friendly format will be implemented upon student request.

 The course is divided into 6 credits: 5 CFU of frontal teaching and 1 CFU of laboratory

The course consists of:

- lecture lectures with classroom slide shows and interactive discussions with students on specific topics. 

- laboratory exercises

Good knowledge of the structure and reactivity of organic compounds.

Attendance in the course is compulsory, with the student having to attend at least 70% of the total course hours for both face-to-face lectures and laboratory classes (see teaching regulations section 3.1)

Introduction 

Application and economic relevance of natural compounds. Primary and secondary metabolites. The 'biosynthetic building blocks. Structural variety and biosynthetic kinship among various groups of natural compounds. Analogues and semisynthetic derivatives of natural compounds.

Medicinal Chemistry and Drug Discovery 

Guiding compounds, drugs, medicines. Origins of 'Medicinal Chemistry. Drug discovery and drug development. Empirical and rational methods. Identification of lead compounds. Bioguided chromatography. Pharmacokinetics and pharmacodynamics. Structure-activity relationships (SAR): opioids, paclitaxel. Lipophilicity and log P. Molecular Graphics.

Receptors, agonists and antagonists 

Enzymes and diseases. Enzyme inhibitors. Reversible and irreversible inhibitors. Competitive, non-competitive and acompetitive inhibitors. Examples of reversible inhibitors: sulfa drugs; ACE inhibitors; statins; steroid 5-a-reductase inhibitors; AchE inhibitors; ribosomal peptidyl transferase inhibitors. Examples of irreversible inhibitors: b-lactamic antibiotics; COX inhibitors.

Enzyme inhibitors 

Enzymes and diseases. Enzyme inhibitors. Reversible and irreversible inhibitors. Competitive, non-competitive and acompetitive inhibitors. Examples of reversible inhibitors: sulfa drugs; ACE inhibitors; statins; steroid 5-a-reductase inhibitors; AchE inhibitors; ribosomal peptidyl transferase inhibitors. Examples of irreversible inhibitors: b-lactam antibiotics; COX inhibitors. DNA-interacting agents: intercalants and minor groove binders; topoisomerase inhibitors, DNA and RNA polymerase inhibitors

Metabolism of Xenobiotics 

Xenobiotics. AMES. Phase I and Phase II enzymes. Oxidases. Cytochrome P450. Oxidation of aromatic compounds. Epoxidation of alkenes. Oxidation of carbons in a to sp2 carbons. Oxidative aromatization. Oxidative dealkylation. CYP450 and drug-drug interaction. Phase II enzymes. Conjugation with glutathione. Glucuronidation. Sulfation. N-acetylation. Esterification with lipids. Methylation. Examples of drug metabolism. 

Chemoprevention of cancer 

Oxidative damage to biological macromolecules. Antioxidants. Chemopreventive agents. Anti-initiators. Anti-promoters. Antiproliferative and inducers of apoptosis. 

Acetate biogenetic pathway 

Biosynthesis of fatty acids. Unsaturated acids. Prostaglandins, thromboxanes and leukotrienes.

Aromatic polyketides. Biosynthesis of aromatic systems and radical coupling. Active principles of Hypericum and Senna. Aflatoxins and microbial contamination of foods. Mycophenolic acid and immunosuppressants. Macrolide and aminoglycoside antibiotics. Anthracyclines. Mycotoxins.

Biogenetic pathway of mevalonate 

Terpenoids. Hemiterpenoids. Irregular monoterpenes: pyrethrins and derived insecticides. Monoterpenoids: constituents of essential oils and fragrances; industrial synthesis of menthol. Oleuropein and hydroxytyrosol. Camphor. Sesquiterpenoids: artemisinin and antimalarials. Gossypol. Diterpenoids: vitamin A. Triterpenoids; nortriterpenoids. Carotenoids: industrial synthesis of b-carotene. Steroids: synthesis of progesterone and corticosteroids. Cardenolides and cardiotonic drugs.

The shikimate biogenetic pathway and polyphenols 

Biosynthesis of shikimic acid and related compounds. Phenolic acids. Biosynthesis of phenylpropanoids. Constituents of essential oils from spices. Polyphenols in foods. Salicylic acid and aspirin. Oleocanthal and anti-inflammatory properties of olive oil. Coumarins and dicumarol.

Oxidative coupling in the biosynthesis of lignans and neolignans. Podophyllotoxin; synthesis of etoposide. Biosynthesis of stilbenoids and flavonoids. Resveratrol: properties and occurrence in foods and beverages. Synthesis of stilbenoids. Flavonoids; flavanones (antioxidants and bittering agents). Green tea flavanols (catechins). Anthocyanins in foods and drinks. Biosynthesis of isoflavonoids. Isoflavonoids (phytoestrogens). Hydrolyzable and condensed tannins.

Alkaloids (34 - 40) 

Medicinal properties of alkaloids. Alkaloids from nicotinic acid: nicotine, arecholine (stimulants).

Mannich reactions in the biosynthesis of alkaloids. Alkaloids from ornithine-phenylalanine: hyoscamine (atropine), cocaine and other tropane alkaloids. Biomimetic synthesis of cocaine. A. derived from phenylalanine: ephedrine and synthetic analogues (amphetamines); cathinone; psychotropic euphoria. Antimitotics: colchicine. Tryptophan-derived alkaloids: serotonin and analogs. Antitumor indolic-terpenoid alkaloids. Tryptophan-derived alkaloids: a. pyrroloindoles (physostigmine). Ergot alkaloids; LSD. Quinoline alkaloids: quinine and analogs (antimalarials). Camptothecin (anticancer).

Tyrosine-derived alkaloids: phenethylamines, catecholamines, mescaline. Opium alkaloids and synthetic analogues. (Narcotics and analgesics). Methadone synthesis. Alkaloids from other biosynthetic pathways: taxol and analogues. A. purines: nerve drinks. Antimetabolites.

Other natural bioactive compounds and their synthetic analogues 

Antiviral drugs. Cyclopeptides. Sulfur compounds in food sources: flavorings, antithrombotic agents, anticancer agents. Glucosinolates. Halogenated compounds. 

Laboratory 

1. Paul M. Dewick, Chimica, Biosintesi e Bioattività delle Sostanze Naturali, 2a Ediz.,Piccin

2. Richard B. Silverman, The Organic Chemistry of Drug Discovery and Drug Action, 2nd edition, Elsevier – Academic Press

3. Richard B. Silverman, Mark W. Holladay, Manuale di Chimica Farmaceutica, Edra SpA 2015

4. Course slides (see: course materials available on STUDIUM).

The student is required to submit a written report related to the laboratory experience.

The exam will be conducted as an oral examination.

The final grade will be based on the following criteria:

Grade 29–30 with honors:

  The student has an in-depth knowledge of the chemistry of natural compounds, biosynthetic processes, and synthesis strategies; is able to describe a process thoroughly, promptly, and accurately; can critically analyze and integrate the questions presented; can independently solve even highly complex chemical problems; and demonstrates excellent communication skills and command of scientific language.

Grade 26–28:

  The student has a good knowledge of the chemistry of natural compounds, biosynthetic processes, and synthesis strategies; is able to describe a process and analyze the presented questions in a clear and reasonably critical way; can solve chemical problems with a fair level of independence; and presents the topics clearly using appropriate terminology.

Grade 22–25:

  The student has a fair knowledge of the chemistry of natural compounds, biosynthetic processes, and synthesis strategies, although limited to the main topics; is able to describe a process and analyze chemical problems with some critical insight, though not always coherently; and presents topics fairly clearly with an adequate command of language.

Grade 18–21:

  The student demonstrates the minimum required knowledge of the chemistry of natural compounds, biosynthetic processes, and synthesis strategies; has a limited ability to describe a process and to critically analyze the situations presented; and explains the topics in a sufficiently clear manner, though with weak language proficiency.

Exam not passed:

  The student does not possess the minimum required knowledge of the main contents of the course. The ability to use specific scientific language is very poor or absent, and the student is unable to apply the acquired knowledge independently.

ADME; Pro-drugs: prontosil ; Flavonoid biosynthesis; Tannins; Menthol synthesis; etc.