COMPOSTI NATURALI PER L'INDUSTRIA FARMACEUTICA E AGROALIMENTARE

The course aims to provide the student with essential knowledge about biosynthesis, properties, and biological and application relevance of natural bioactive compounds, including some examples of industrial synthesis. This course will also provide basic knowledge on interaction with receptors and enzymes, xenobiotics' metabolism, and nutraceuticals' role in nutrition. Upon completion of the course, the student should acquire reasoning skills and independent judgment on the specific topics of the teaching and be able to discuss each topic with the scientific method and appropriate language.

In addition, regarding the so-called Dublin Descriptors, this course contributes to the acquisition of the following transversal skills:
D1 - Knowledge and Ability to Understand: The student should be able to rationalize the property-structure correlations of natural compounds and their synthetic analogues. Inductive and deductive reasoning skills.
D2 - Ability to apply knowledge and understanding: The student should demonstrate the ability to interpret the phenomena described in the course concerning the chemical properties of natural compounds and the synthesis of analogues. The student should demonstrate the ability to the possible applications of natural compounds or their synthetic analogues in the pharmaceutical, nutritional and agronomic fields based on biological properties.
D3 - Autonomy of judgment: students should be able to design and conduct experiments independently. By the end of the course, they should be able to interpret the collected data coherently, critically and correctly, correlating them with appropriate theories; in addition, they should formulate hypotheses and discard incorrect ones.
D4 - Communication Skills: The student should be able to communicate with propriety of language and terminological rigour, a scientific topic, explaining the reasons and results.
D5 - Learning skills: students should be able to develop the ability to use appropriate models to describe the properties of natural compounds or their synthetic analogues.

Information for students with disabilities and/or SLD
To guarantee equal opportunities and in compliance with the laws in force, interested students can ask for a personal interview in order to plan any compensatory and/or dispensatory measures, based on the didactic objectives and specific needs.

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 
Extraction techniques of bioactive compounds, solvent extraction, vacuum filtration, column chromatography, thin layer chromatography (TLC), bio-guided fractionation.

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

2. Richard B. Silverman, The Organic Chemistry of Drug Discovery and Drug Action, 2^nd 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).

Students are required to submit a paper related to the laboratory experience. The examination will be conducted according to an Oral Examination.

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