Medicinal Chemistry and Bioprocesses

A.Y. 2019/2020
10
Max ECTS
80
Overall hours
SSD
CHIM/08 CHIM/11
Language
Italian
Learning objectives
The course of Pharmaceutical Chemistry and Bioprocesses, included in the educational plan of the Pharmaceutical curriculum of the Degree Course in Biotechnology, aims to provide the student with:
a) the knowledge that underlies the design and development of new active ingredients having the required requisites to be able to become drug candidates.
b) the concepts necessary to understand the principles that regulate the fermentation processes in the production of drugs of natural or biotechnological origin.
Furthermore, through the description and in-depth analysis of some classes of drugs and all the steps required for setting up a process on an industrial scale, the course aims to provide students with the elements necessary to understand the critical issues that can be found in the entire process leading to the production and development of a drug.
Expected learning outcomes
Students will have to demonstrate that they have acquired and understood:
a) the basic concepts of pharmaceutical chemistry, the notions provided on the chemical, chemical-physical, structural properties and on the mechanism of action of drugs belonging to the main therapeutic classes, the fundamental elements of drug design and the role that the new biotechnological drugs have in research and development processes.
b) all the notions necessary for the preparation of a biotechnological process starting from the selection of the strain, to the study of the biosynthetic path, to the improvement of the stocks up to the development of the fermentation process and the recovery of the product.
Thanks to the notions provided in the lectures and the exercises carried out in the classroom, the students will be able to independently analyze the critical points of the process and will learn to hypothesize and design a fermentation process in its different phases, depending on the producer microorganism and the desired metabolite. Students must also be able to correctly understand the questions in the learning verification phase, to know how to choose, process and connect the knowledge acquired in both modules of the course.
Course syllabus and organization

Single session

Lesson period
First semester
Course syllabus
During the lectures on Pharmaceutical Chemistry the following topics will be chronologically illustrated:
1 Introduction to Medicinal Chemistry:
The discovery and development of new drugs. Biotechnology for the discovery and development of new drugs
Molecular mechanisms of drug action and drug targets
Receptors as targets for drugs
Enzymes as targets for drugs
Nucleic acids as targets for drugs
2. Drug design and development:
Sources of research for lead compounds.
New "Drug design" strategies
Structure-activity relationships (SAR). Pharmacophore research.
Optimization of drug interaction with the target. Chemical similarity.
Bioisosteric and stereochemical aspects of drug action.
Chemical-physical and biopharmaceutical properties of drugs and pharmacokinetics
Drug design aimed at optimizing drug access to the target
Prodrugs.
Quantitative Relationships Structure-Activity (QSAR)
3. Notes on combinatorial chemistry, in particular for peptide synthesis.
During the discussion of the aforementioned topics, numerous references will be made to various types of drugs. In particular, the following classes of drugs will be explored:
· Antibiotics
· Anti-cancer drugs (selected examples).

With regard to the part of the course concerning the fermentation processes in the production of drugs, the following topics will be treated:
1. Fermentation process flow sheet: upstream and downstream
2. Microorganisms selection: screening, primary and secondary test, library construction and their characteristics
3. Characteristics of industrial strains and their conservation. Microorganisms of industrial interest for the production of secondary metabolites of pharmaceutical interest: actinomycetes and fungi. Yeasts and bacteria of industrial interest for the production of heterologous proteins: Pichia pastoris, Saccharomyces cerevisiae, Escherichia coli. Strain improvement.
4. Secondary metabolism in relation to the production of biologically active molecules. Characteristics, correlation with primary metabolism, regulation and catabolite repression. Gene clusters and general patterns of metabolic pathways
5. Upstream i) preparation of master and working cells banks, ii) inoculum,: vegetative, fermentative, chemically defined and complex culture medium, iii) raw carbon and nitrogen sources (molasses, corn steep liquor ...), growth factors, anti-foam. Development of industrial culture mediums. Case study.
6. Selection of the type of culture: solid, semi-solid, submerged, stationary. Fermenters: general characteristics, process variables, temperature control, agitation, aeration, sensors. Sterilization and pre-fermentation line.
7. Description of the fermentative processes through the Gaden curves, growth curves in relation to the production of primary and secondary metabolites. Batch, fed-batch and continuous processes. Productivity.
8. Dowmstream: general considerations about the choice of recovery techniques on industrial scale. Solid-liquid separation, primary isolation, high-resolution purification and formulation.
Prerequisites for admission
To adequately address the contents of the course it is necessary that the student has the basic knowledge of microbiology and has a good knowledge of organic chemistry and biological chemistry.
Teaching methods
The course includes lectures during which will also be carried out exercises based on case studies and quiz exam simulations to verify the understanding of the topics covered.
Teaching Resources
All the teaching material shown during the lectures and the scientific literature will be made available to students on the Ariel platform.
Students will learn more about the topics covered using the following texts:
1. G. L. Patrick: an introduction to Medicinal Chemistry. 6th Ed. - Oxford University Press (2017). ISBN: 978-0-19-874969-1.
2. G. L. Patrick: Chimica Farmaceutica, III Ed. EdiSES- Napoli (2015). ISBN: 978-88-7959-845-3.
3. S. Donadio, G. Marino: Biotecnologie Microbiche - Casa Editrice Ambrosiana
Possible additional material will be provided by the teachers during the lessons
Assessment methods and Criteria
The exam will be divided into a written and an oral test.
The written test, lasting 120 minutes, will normally be divided into two parts.
The first part will include 1-2 open questions concerning the topics included in the program of Bioprocesses for drug preparation and a planning exercise of a fermentation process.
The second part will consist on 1-2 open questions and a multiple choice questionnaire concerning the "Medicinal Chemistry" program.
To access the oral exam it will be necessary to obtain an assessment of at least 18/30 in both parts of the written test.
The oral test will take place no later than 10 days after the written test and will include a discussion of the written exam with possible in-depth analysis of the topics covered.
The vote, expressed in thirtieths, will be determined by a weighted average of the vote attributed by the two teachers.
Attending students will have the opportunity to take mid-term tests at the end of the lessons given by each teacher. In this case the evaluation expressed in thirtieths will be determined by a weighted average of the marks obtained in the two tests in progress.
The evaluation will be carried out considering the student's ability to correctly understand the questions and to choose, elaborate and connect the knowledge acquired during the course, using an appropriate scientific language.
Bioprocesses for drug preparation
CHIM/08 - PHARMACEUTICAL CHEMISTRY - University credits: 0
CHIM/11 - CHEMISTRY AND BIOTECHNOLOGY OF FERMENTATION - University credits: 0
Lessons: 32 hours
Professor: Gandolfi Raffaella
Medicinal Chemistry
CHIM/08 - PHARMACEUTICAL CHEMISTRY - University credits: 0
CHIM/11 - CHEMISTRY AND BIOTECHNOLOGY OF FERMENTATION - University credits: 0
Lessons: 48 hours