ECTS credits ECTS credits: 4.5
ECTS Hours Rules/Memories Hours of tutorials: 4 Expository Class: 20 Interactive Classroom: 21 Total: 45
Use languages Spanish, Galician
Type: Ordinary Degree Subject RD 1393/2007 - 822/2021
Departments: Organic Chemistry
Areas: Organic Chemistry
Center Faculty of Pharmacy
Call: Second Semester
Teaching: With teaching
Enrolment: Enrollable
The subject Drug Design is based on the study of various strategies used in drug development, as well as the prediction of new therapeutic agents with improved activity or reduced toxicity.
The course objectives are as follows:
• To study the physicochemical foundations of drug action at the molecular level, along with the main structural parameters that influence their activity.
• To understand the major therapeutic targets and how to modulate drug-receptor interactions, as well as to design prodrugs and/or bioprecursors that improve pharmacokinetic properties.
• To interpret biological results and establish structure-activity relationships (SAR) that enable the prediction of new drug candidates.
• To become familiar with key computer-aided drug design (CADD) techniques.
BLOCK I. BASIC CONCEPTS OF DRUG DESIGN
Topic 1. Evolution of methods for discovering new drugs.
From serendipitous discovery to systematic search. General overview.
Topic 2. Methods for identifying new lead compounds I.
Classical methods. Structural modification of natural products. Bioassays of compounds and libraries. Clinical observations: side effects. Study of drug metabolites. Synthesis intermediates.
Topic 3. Identification of lead compounds II.
Combinatorial chemistry. Design of compound libraries.
Topic 4. Identification of lead compounds III.
Structure-based drug discovery. Database screening.
BLOCK II. RATIONAL DESIGN TARGETING THE RECEPTOR
Topic 5. Chemical nature and types of biological targets.
Receptors. Chemical structure of biomacromolecules. Proteins and nucleic acids. Three-dimensional structure.
Topic 6. Drug–receptor interaction.
Physicochemical and structural aspects. Electrostatic, non-polar, and hydrophobic interactions. Topological factors.
Topic 7. Chirality and its influence on pharmacodynamics.
Isomeric differences in activity, antagonism, or selectivity. Eudismic ratio.
Topic 8. Pharmacomodulation.
Structural disjunction and conjunction. Homology. Vinylogy. Ring transformations. Conformational restriction.
Topic 9. Structure variation through isosterism.
Bioisosteric modifications. Bioisosterism criteria. Classical and non-classical bioisosterism.
BLOCK III. RATIONAL DESIGN AND PHARMACOKINETICS
Topic 10. Chemical modulation of pharmacokinetics I.
Physicochemical properties and pharmacological activity. Overview. Drug transport. Solubility. Ionization degree. Partition coefficient. Protein binding. Effects of stereochemistry on ADME.
Topic 11. Chemical modulation of pharmacokinetics II.
Modulating absorption. Strategies to cross the blood-brain barrier. Membrane transporters. Modulating distribution. Plasma stability. Plasma protein binding.
Topic 12. Prodrug design.
Prodrugs and the concept of protecting groups. Metabolic stability. Hard and soft drugs.
Topic 13. The prodrug–bioprecursor principle.
Chemical mechanisms of bioactivation: hydrolysis, reduction, oxidation.
Topic 14. Drug metabolism and its modulation.
Phase I and II metabolic transformations. Chemical aspects of toxic biotransformations. Modulating CYP450 inhibition.
Topic 15. Enzyme inhibition as a drug design strategy.
Stereoselectivity. Transition state inhibitors. Suicide inhibitors.
Topic 16. Drug selectivity. Multi-target drugs.
Current strategies in lead discovery. Lipinski’s rule of five.
BLOCK IV. COMPUTER-AIDED DESIGN
Topic 17. Introduction to basic molecular modeling and visualization tools.
Macromolecule visualization: DNA and proteins. Access to the Brookhaven Protein Data Bank.
Topic 18. Three-dimensional structure and molecular modeling.
Small molecule modeling. Geometric optimization. Conformational analysis. Superposition/comparison. Similarity criteria. Molecular fitting.
Topic 19. Drug–receptor interaction visualization.
Comparison methods. Molecular docking.
Topic 20. Quantitative Structure–Activity Relationship (QSAR).
Molecular descriptors. Hydrophobic, electronic, and steric parameters. Topological parameters. Calculation methods.
Topic 21. Data analysis.
Discriminant analysis. Regression analysis. QSAR methodologies. Hansch analysis.
Topic 22. De novo design methods.
Free–Wilson analysis. Training series design. Craig, Topliss, Fibonacci, and Simplex methods.
Topic 23. Neural networks.
Virtual screening. In silico prediction of activity/toxicity.
BASIC:
1. Introducción a la Química Farmacéutica. Editado por Mª del Carmen Avendaño. McGraw-Hill/Interamericana, S.A., 2ª edición. Madrid (2001).
2. Foye's principles of medicinal chemistry. Sixth Edition, by Thomas L. Lemke and David A. Williams. Lippincott Williams & Wilkins, Philadelphia (USA) (2008)
3. The Practice of Medicinal Chemistry, 3 Ed. by Camille Georges Wermuth. Academic Press-Elsevier, Amsterdam (Holanda) (2008).
4. Wilson and Gisvold’s Textbook of Organic Medicinal and Pharmaceutical Chemistry. 11 Ed. by John H. Block and John M. Beale. Lippincott Williams & Wilkins, Philadelphia (USA) (2004).
5. Recursos "on line"
COMPLEMENTARY:
1. The Organic Chemistry of Drug Design and Drug Action, 2 Ed. by Richard B. Silverman, Academic Press, (2004)
2. Introduction to the principles of drug design and Action, 4 Ed. by Smith and Wiliams´. John Smith, CRC Press (2011)
3. Textbook of drug design and discovery, by Povl Krogsgaard-Larsen, Kristian Strømgaard, and Ulf Madsen, 4th ed. CRC Press (2011)
4. Pharmacokinetics and metabolism in drug design, (Methods & Principles in Medicinal Chemistry), 3 Ed. by Douglas A. Smith, Charlotte Allerton, Amit S. Kalgutkar y Han van de Waterbeemd Weinheim : Wiley-VCH, cop. 2012
5. Drugs: From Discovery to Approval. 2 Ed. by Rick Ng. Wiley-Blackwell, New Jersey, (USA) (2009).
6. Computational Medicinal Chemistry for Drug Discovery, by Patrick Bultinck, Marcel Dekker, 2004.
Con 01. Understand the origin, nature, and how to design, obtain, analyze, control, and produce active pharmaceutical ingredients, drugs, and medicines, as well as other products and raw materials of health interest for human or veterinary use.
Con 11. Understand the physicochemical properties of substances used in drug manufacturing.
Con 12. Understand the characteristics of reactions in solution, the different states of matter, and the principles of thermodynamics and their application to pharmaceutical sciences.
Con 13. Understand the characteristic properties of elements and their compounds, as well as their application in the pharmaceutical field.
Con 14. Understand the nature and behavior of functional groups in organic molecules.
Con 15. Understand the principles and procedures for the analytical determination of compounds: analytical techniques applied to the analysis of water, food, and the environment.
Con 16. Know and apply the main techniques of structural investigation, including spectroscopy.
Skills or Abilities:
H/D 07. Select appropriate techniques and procedures for the design, application, and evaluation of reagents, methods, and analytical techniques.
H/D 08. Carry out standard laboratory processes, including the use of scientific synthesis and analysis equipment, with appropriate instrumentation.
H/D 09. Estimate the risks associated with the use of chemical substances and laboratory processes.
Competencies:
Instrumental Competencies:
Comp 05. Basic computer skills.
Comp 06. Information management skills (ability to search and analyze information from various sources).
Comp 07. Problem-solving skills.
Comp 08. Decision-making skills.
Interpersonal Competencies:
Comp 14. Ability to communicate with experts from other fields.
Systemic Competencies:
Comp 19. Research skills.
Comp 20. Learning ability.
Comp 22. Ability to generate new ideas (creativity).
Theoretical teaching: 23 h
Interactive seminar teaching: 14 h
Interactive teaching in laboratory/computer classroom: 4 h
Individual student tutoring: 2 h
Exams and review: 2 h
Student personal work: 67.5 h
A) Lecture
Primarily aimed at the professor presenting the theoretical foundations of the subject in sessions of approximately one hour each. The professor will deliver these lectures using audiovisual and computer aids. Attendance is recommended and will be considered as part of the evaluation.
B) Interactive seminar classes. Problem-solving.
Theoretical/practical classes where questions related to theory lessons and exercises are proposed and solved. The student will actively participate in these classes, mainly through involvement in debates, preparation of assignments based on prior knowledge (articles, websites, etc.), and solving exercises. Attendance and student attitude will be considered as part of the evaluation.
C) Tutorials: Scheduled by the professor.
These will be scheduled by the professor and dedicated to activities that assess the level of learning and understanding of the subject. Clarification of doubts about theory or practice, problems, exercises, or other proposed tasks. The student must participate actively and will complete an assessment related to material provided by the professor in advance. Attendance and student attitude will be considered part of the evaluation.
D) Practical sessions/computer classroom
These complement the theoretical classes given to a large group. The student will gain skills in those parts of the program that are primarily theoretical/practical, referred to as Block IV. These contents will be addressed using computers and the necessary software. Sessions of 2 hours are planned, and the student must submit a report on the work done, which will be considered part of the evaluation. Attendance in computer classes is mandatory and will be considered an evaluation criterion. To carry out the practical work, the student must have their own personal PC.
E) Classroom presentation (of a project, exercise, etc.). Discussion forums - group work - collaborative learning.
EVALUATION SYSTEM
Exam. MINIMUM WEIGHTING: 50% MAXIMUM WEIGHTING: 100%
Seminars. Problem-solving/exercises - continuous assessment MINIMUM WEIGHTING: 0% MAXIMUM WEIGHTING: 50%
Laboratory/computer practicals: MINIMUM WEIGHTING: 0% MAXIMUM WEIGHTING: 50%
Oral presentation (additional activities included in continuous assessment): MINIMUM WEIGHTING: 0% MAXIMUM WEIGHTING: 50%. Debate: MINIMUM WEIGHTING: 0% MAXIMUM WEIGHTING: 50%
The evaluation of the knowledge, skills, and competencies acquired in the subject will be carried out through the following means:
In the theoretical exam: With 1, 11, 12, 13, 14, 15, Competency 07, Competency 20.
In the evaluation of laboratory practicals and oral presentations: With 16, H/D 07, H/D 08, H/D 09, Competency 05, 06, 14, 19, 22.
In the evaluation of interactive classes: H/D 07, H/D 08, Competency 07, 08, 09, Competency 20, 22.
The student's overall grade, out of a total of 10 points, will be the sum obtained according to the following distribution:
Continuous assessment of the student’s participation and attitude during in-person hours (seminars, tutorials), including the presentation of a group project in which the competencies acquired both in theory and computer practicals will be evaluated, will contribute a minimum of 3 points, equivalent to 30% of the final grade. Attendance at lectures is recommended, but not mandatory.
Completion of computer practicals is mandatory (attendance and group work preparation); if the student does not attend the practicals, the final grade for the subject will be "fail." Passing the practical classes in a given academic year will be valid for all exam sessions of that year and also for the two subsequent academic years. The continuous assessment grade may be retained for repeating students who wish to keep it.
The evaluation of knowledge through exams will contribute a maximum of 7 points (70% of the final grade) and will consist of two exams:
The theoretical exam will be carried out in two phases.
The first phase will cover the content of the first third of the program and contribute a maximum of 3 points (30%), with a minimum score of 1.5 out of 3 required.
The second phase will include the content of the remaining topics and contribute a maximum of 4 points (40%), with a minimum score of 2 out of 4 required.
For the total theoretical exam, a minimum of 3.5 points out of 7 must be achieved to add to the continuous assessment grade.
In the second exam opportunity, students who do not reach at least 1.5 points out of 3 in the first part, or 2 points out of 4 in the second part, will not be able to compensate their grade with other sections.
To pass the subject, the total sum of grades must be at least 5 points out of 10.
In the second opportunity exam (June or July), students will only be tested on theoretical content, since grades obtained in continuous assessment will be retained for the final grade calculation.
The evaluation of students exempt from attending class will be done solely based on the exam grade, which will consist of two parts: the first will count for a maximum of 4 points and the second part for 6 points, with a minimum of 50% required in each part. There are two exam opportunities and one session per academic year.
In case of fraudulent use during exercises or tests, the regulations established in the Academic Performance and Grade Review Policy will be applied.
Individual or group autonomous study: 46 hours
Solving exercises or other work related to seminar classes: 6 hours
Guidance and doubt resolution for tutorials: 2.5 hours
Preparation of work and databases related to computer practicals: 10 hours
Taking and reviewing the exam: 3 hours
The student must:
Show an open and unbiased attitude toward the subject, objectively analyzing its relevance within the context of their professional and overall education.
Try to solve the questions posed in the lectures in order to be able to raise questions in the interactive classes.
It is advisable to attend all classes for effective learning, efficient training, and to obtain a positive evaluation in the subject.
Study the material continuously.
Online resources necessary for the proper development of the subject:
For preparing the subject, it is important to use the resources available on the web: free software, tutorials, etc., with access links that will be updated by the professor at the beginning of the course. Among others:
Protein Data Bank: http://www.rcsb.org/pdb/
Design: http://www.drugdesign.org
SwissPDBViewer, SwissADME, Arguslab, UCSF Chimera, ChimeraX
Attendance at lectures, while not mandatory, is highly recommended to achieve adequate performance in interactive teaching.
Active participation in interactive teaching.
Consultation of bibliographic and informational sources.
Any student who does not successfully pass the evaluation process and wishes to do so may contact the professor during tutoring hours for advice related to the subject.
Alberto José Coelho Cotón
Coordinador/a- Department
- Organic Chemistry
- Area
- Organic Chemistry
- Phone
- 881814941
- albertojose.coelho [at] usc.es
- Category
- Professor: University Lecturer
Wednesday | |||
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13:00-14:00 | Grupo /CLE_01 | Spanish | 5035 Classroom 6 Faculty of Law |
Thursday | |||
13:00-14:00 | Grupo /CLE_01 | Spanish | 5035 Classroom 6 Faculty of Law |
Friday | |||
13:00-14:00 | Grupo /CLE_01 | Spanish | 5035 Classroom 6 Faculty of Law |