30 November 2008
Lecture on 20/12/2008 at 11.30am for all
The lecture of antioxidants and antiaging drugs will be held on Saturday 20 December 2008 at 11.30 am-1.30 pm at Ragab Fahmy for all students.
22 October 2008
Fourth lecture 20/10/2008
You have to point out the following:
1- Structure of the drug molecule affects the biological ativity in two ways: first, it affects its affinity to the receptor; second, it affects its physicochemical properties and hence its pharmacokinetics.
2- The relation between structure and physicochemical properties (PCP) can be quantified ((QSAR)) through the Hansch equation.
3- The relation between activity and partition coefficient (PC) is parabolic and not linear.Why?
4- π and σ are descriptors of the hydrophobic and electronic effects of substituents. They can have either +ve or -ve values. What is the significace of π and σ values?
5- Topliss scheme is generated through interactive SAR studies. It indicates whether activity favours increased or decreased lipophilicity; favours electron withdrawing or electron donating groups. The various chemical groups are arranged in what is called Craig plot (a 2 dimensional plot) to easily locate the π and σ values of groups.
6- Steric factors can be measured by two experimental methods and one computational method.
7- Experimental determination of π depends on the fact that the sum of π values of the groups constituting the molecule represents the PC.
8- Experimental determination of σ value depends on the effect of electron withdrawing or electron donating properties of a given group on the acidity (pKa) of benzoic acid.
9- Experimental determination of Es depends on the effect of a given group (larger than methyl) on the rate of hydrolysis (K) of substituted methylacetate.
The Hansch equation relating π, σ and Es is:
Log 1/C= -K π2+K’ π+ σρ+K’’Es+K’’’
Molar refractivity MR=
1- Structure of the drug molecule affects the biological ativity in two ways: first, it affects its affinity to the receptor; second, it affects its physicochemical properties and hence its pharmacokinetics.
2- The relation between structure and physicochemical properties (PCP) can be quantified ((QSAR)) through the Hansch equation.
3- The relation between activity and partition coefficient (PC) is parabolic and not linear.Why?
4- π and σ are descriptors of the hydrophobic and electronic effects of substituents. They can have either +ve or -ve values. What is the significace of π and σ values?
5- Topliss scheme is generated through interactive SAR studies. It indicates whether activity favours increased or decreased lipophilicity; favours electron withdrawing or electron donating groups. The various chemical groups are arranged in what is called Craig plot (a 2 dimensional plot) to easily locate the π and σ values of groups.
6- Steric factors can be measured by two experimental methods and one computational method.
7- Experimental determination of π depends on the fact that the sum of π values of the groups constituting the molecule represents the PC.
8- Experimental determination of σ value depends on the effect of electron withdrawing or electron donating properties of a given group on the acidity (pKa) of benzoic acid.
9- Experimental determination of Es depends on the effect of a given group (larger than methyl) on the rate of hydrolysis (K) of substituted methylacetate.
The Hansch equation relating π, σ and Es is:
Log 1/C= -K π2+K’ π+ σρ+K’’Es+K’’’
Molar refractivity MR=
16 October 2008
Third lecture 13/10/2008
By the end ofthe lecture and tutorial you should be able to:
1- Recognize the role of mol.modeling in simulating the real drug-receptor interactions and thereby helping the medicinal chemist in designing more rationale ligands.
2- understand that the main target of mol.modeling is to maximize the output of active drugs after a reasonable laboratory work, time, and cost.
3- know the two types of CALD (structure-based and lignd-based; differences??).
4- Differentiate beween a ligand and a drug; lowest energy conformation of a drug and its bioactive conformation; pharmacophore identificaton in structure-based and lignd-based dug design)
5- Docking or fitting is judged according to the calculated binding energies that are compared to a reference drug. It is all computerized process.
6- The importance of docking validation.
7- Imagine how small is the binding site of a receptor or enzyme compared to the whole receptor or enzyme protein.
8- Understand that the pharmacophore of the binding site is a 3D arrangement of a group of aminoacids to which complementary groups in the ligand molecule will bind.
9- Understand that the conformation of the binding site acquired after drug-receptor interaction determines the kind of action (agonist or antagonist) and that each biological action is elicited by a certain characteristic conformation (bioactive conformation of the receptor). Therefore, the 3D pharmacophore of the receptor I work on (obtained from PDB) should be that of the biological action I design a drug for.
Here are some T/F questions:
1- In all cases, results of virtual screening using CAMM match those obtained from biological screening.
2- Hypothetical receptor site model is generated whenever the biological target is unknown.
3- The bioactive conformation of a drug is sometimes different from its lowest energy conformation.
4- A 3D pharmacophore represents the relative positions of the important binding groups connected in a defined skeleton.
5- Recognition of the binding site of an enzyme is done by co-crystallization of the enzyme with its specific substrate.
6- In direct drug design, pharmacophore triangles are developed as templates for comparison with candidate drug.
7- DISCO is a computer software used for predicting molecular superimposition.
8- Docking occurs when the new drug molecule interacts optimally with the target protein structure.
The answers are F,T,T,F,T,F,T,T.
Here are links to RCSB proteindata bank:
http://pdbbeta.rcsb.org/pdb/home/home.do;jsessionid=A6C94FB066E4EDC56AB051093D03D871
and to Arguslab (a free molecular modeling software):
http://www.arguslab.com/
1- Recognize the role of mol.modeling in simulating the real drug-receptor interactions and thereby helping the medicinal chemist in designing more rationale ligands.
2- understand that the main target of mol.modeling is to maximize the output of active drugs after a reasonable laboratory work, time, and cost.
3- know the two types of CALD (structure-based and lignd-based; differences??).
4- Differentiate beween a ligand and a drug; lowest energy conformation of a drug and its bioactive conformation; pharmacophore identificaton in structure-based and lignd-based dug design)
5- Docking or fitting is judged according to the calculated binding energies that are compared to a reference drug. It is all computerized process.
6- The importance of docking validation.
7- Imagine how small is the binding site of a receptor or enzyme compared to the whole receptor or enzyme protein.
8- Understand that the pharmacophore of the binding site is a 3D arrangement of a group of aminoacids to which complementary groups in the ligand molecule will bind.
9- Understand that the conformation of the binding site acquired after drug-receptor interaction determines the kind of action (agonist or antagonist) and that each biological action is elicited by a certain characteristic conformation (bioactive conformation of the receptor). Therefore, the 3D pharmacophore of the receptor I work on (obtained from PDB) should be that of the biological action I design a drug for.
Here are some T/F questions:
1- In all cases, results of virtual screening using CAMM match those obtained from biological screening.
2- Hypothetical receptor site model is generated whenever the biological target is unknown.
3- The bioactive conformation of a drug is sometimes different from its lowest energy conformation.
4- A 3D pharmacophore represents the relative positions of the important binding groups connected in a defined skeleton.
5- Recognition of the binding site of an enzyme is done by co-crystallization of the enzyme with its specific substrate.
6- In direct drug design, pharmacophore triangles are developed as templates for comparison with candidate drug.
7- DISCO is a computer software used for predicting molecular superimposition.
8- Docking occurs when the new drug molecule interacts optimally with the target protein structure.
The answers are F,T,T,F,T,F,T,T.
Here are links to RCSB proteindata bank:
http://pdbbeta.rcsb.org/pdb/home/home.do;jsessionid=A6C94FB066E4EDC56AB051093D03D871
and to Arguslab (a free molecular modeling software):
http://www.arguslab.com/
30 September 2008
Second lecture 29/9/2008
By the end of this lecture you have to:
* Understand why there is a difference between the in vivo and in vitro results of biological activity.
* Understand that variation in biological activity is not always a matter of drug-receptor affinity or intrinsic activity.
* Know that bioavailability of the drug is a key factor in determining the therapeutic efficacy of the drug.
* Correlate between drug solubility, pKa, logP and its pharmacokinetic profile (site of action, duration of action,...etc.).
* Know how to, structurally, modify a drug so as to change its physicochemical properties and hence change or improve its therapeutic use.
Here are some T/F questions from previous exams:
1- The physicochemical properties of I.V. general anesthetics are important in that they affect ADME of the drug.
2- Micronized griseofulvin has better dissolution and absorption than regular griseofulvin.
3- High molecular weight dugs are absorbed by convective absorption.
4- Barbital and secobarbital have similar absorption rates since they have similar pKa values.
5- It is always required that drugs have high partition coefficient to ensure better absorption from GIT.
6- Neutral fat, unlike plasma protein, is regarded as a storage site for hydrophobic drugs.
Answers will be:
1- (F) because IV drugs are not absorbed through membrane barriers.
2- (T)
3- (F) it is only low MW drugs that are absorbed by convective absorption.
4- (F) because they differ in their part.coeff.
5- (F) because some drugs are required to act locally in the GIT eg. succinyl sulfathiazole.
6- (T) storage in neutral fat depends on the lipophilicity of the drug but plasma protein binding depends on the structure of the drug not lipophilicity.
* Understand why there is a difference between the in vivo and in vitro results of biological activity.
* Understand that variation in biological activity is not always a matter of drug-receptor affinity or intrinsic activity.
* Know that bioavailability of the drug is a key factor in determining the therapeutic efficacy of the drug.
* Correlate between drug solubility, pKa, logP and its pharmacokinetic profile (site of action, duration of action,...etc.).
* Know how to, structurally, modify a drug so as to change its physicochemical properties and hence change or improve its therapeutic use.
Here are some T/F questions from previous exams:
1- The physicochemical properties of I.V. general anesthetics are important in that they affect ADME of the drug.
2- Micronized griseofulvin has better dissolution and absorption than regular griseofulvin.
3- High molecular weight dugs are absorbed by convective absorption.
4- Barbital and secobarbital have similar absorption rates since they have similar pKa values.
5- It is always required that drugs have high partition coefficient to ensure better absorption from GIT.
6- Neutral fat, unlike plasma protein, is regarded as a storage site for hydrophobic drugs.
Answers will be:
1- (F) because IV drugs are not absorbed through membrane barriers.
2- (T)
3- (F) it is only low MW drugs that are absorbed by convective absorption.
4- (F) because they differ in their part.coeff.
5- (F) because some drugs are required to act locally in the GIT eg. succinyl sulfathiazole.
6- (T) storage in neutral fat depends on the lipophilicity of the drug but plasma protein binding depends on the structure of the drug not lipophilicity.
22 September 2008
First lecture 22/9/2008
Click the following link about the discovery of Captopril
http://en.wikipedia.org/wiki/Captopril
Here are some examples of true/false questions from previous exams:
1- Mechanism-based drug design is a rationale drug design.
2- 5-FU inhibits DNA biosynthesis in cancer cells because of its structure analogy to deoxyguanosine.
3- Mevalonic acid is the natural substrate of HMG-CoA reductase enzyme in cholesterol biosynthesis.
4- The mechanism of the antidiabetic effect of rosiglitasone is not a receptor mediated process.
5- The molecular lead of captopril is the nonapeptide ‘teprotide’.
6- Although, cimetidine is not structurally related to histamine, yet it is a potent H2-receptor antagonist.
The answers are : T, F, F, F, T, F.
After studying the lecture you should:
* Be able to differentiate between traditional and rationale drug design.
* Differentiate between pharmacological action of a drug and its therapeutic application.
*Notice the mimicry (resemblence) between natural metabolites or endogenous components and their antagonists.
*Be able to identify the biological targets (enzyme or receptor) for each drug.
*Know how to modify lead compounds to improve binding of the drug molecule to its target protein. (Example of Captopril,..).
*Relate between the physicochemical properties of a drug (E.g. polymixin) and its mechanism of action.
http://en.wikipedia.org/wiki/Captopril
Here are some examples of true/false questions from previous exams:
1- Mechanism-based drug design is a rationale drug design.
2- 5-FU inhibits DNA biosynthesis in cancer cells because of its structure analogy to deoxyguanosine.
3- Mevalonic acid is the natural substrate of HMG-CoA reductase enzyme in cholesterol biosynthesis.
4- The mechanism of the antidiabetic effect of rosiglitasone is not a receptor mediated process.
5- The molecular lead of captopril is the nonapeptide ‘teprotide’.
6- Although, cimetidine is not structurally related to histamine, yet it is a potent H2-receptor antagonist.
The answers are : T, F, F, F, T, F.
After studying the lecture you should:
* Be able to differentiate between traditional and rationale drug design.
* Differentiate between pharmacological action of a drug and its therapeutic application.
*Notice the mimicry (resemblence) between natural metabolites or endogenous components and their antagonists.
*Be able to identify the biological targets (enzyme or receptor) for each drug.
*Know how to modify lead compounds to improve binding of the drug molecule to its target protein. (Example of Captopril,..).
*Relate between the physicochemical properties of a drug (E.g. polymixin) and its mechanism of action.
21 September 2008
Welcome to 4th year pharmacy students
Welcome to fourth year pharmacy students. I wish you a happy fruitful academic year. Your are first-time students of pharmaceutical and medicinal chemistry. This is an interesting chemistry science that deals with the study of the chemical structures of drugs. The importance of this study lies in that the relation between structure and biological activity is intimate; so that you can predict the activity of an unknown compound just from its chemistry. Also, you can know which structure will be more active than the other. In addition, you can explain many pharmacokinetic and pharmacodynamic properties based on the chemical stucture of the compound. You will also study the principles of drug design and discovery in traditional and in computer-assissted processes. Another important topic in your study includes the understanding and pathways of drug metabolism. Moreover, you will study the methods of synthesis and analysis of different drugs.
Regarding my course, we will enjoy together the study of mechanism-based drug design, computer-aided drug design, physicochemical properties of drugs in relation to their action, and quantitative structure-activity relationships.
You are invited to visit my blog at the end of each week during the course of my lectures as you can find helpful things that will assisst your knowledge and understanding of the course I will teach to you.
Best wishes.
07 April 2008
My C.V.
Curriculum Vitae
Name: Fadi Mohsen Awadallah
Date of birth: 30/12/1971
Nationality: Egyptian
Languages: English and French
Name: Fadi Mohsen Awadallah
Date of birth: 30/12/1971
Nationality: Egyptian
Languages: English and French
Certificates
- B.Sc. (Pharmacy and Pharmaceutical Sciences, Cairo University, Excellent honor, 1993)
- M.Sc. (Pharmaceutical Chemistry, Cairo University, 2000)
MSc thesis entitled:” Synthesis of certain pyranoquinolines as potential antimicrobial agents”; from which one article was published:
”Synthesis of certain pyranoquinolones as potential antimicrobial agents”
Abou-Shady, H.A., Amin, K.M., Hanna, M.M. and Awadallah, F.M.,
Bull.Fac.Pharm.Cairo Univ. (2003), 41(3), 59-73
- Ph.D. (Pharmaceutical Chemistry, Cairo University, 2004)
PhD thesis entitled: ”Synthesis of some pyranoquinolines and related tetracyclic derivatives as potential antineoplastic agents”; from which two articles were published:
“Synthesis of some pyranoquinoline derivatives with anticipated antineoplastic activity”
Amin, K.M., El-Sayed, N.M., Mohammed, S.R. and Awadallah, F.M.,
Bull.Fac.Pharm. Cairo Univ. (2005), 43(3), 87-94
”Synthesis of some new pyranoquinoline derivatives of potential antineoplastic activity”
Amin, K.M., El-Sayed, N.M., Mohammed, S.R. and Awadallah, F.M.,
Egypt.Pharm.J.(2006), 5(1), 157-173
Positions held: *Demonstrator of Pharmaceutical Chemistry, College of Pharmacy, Cairo University, 1994-2000.
*Assistant lecturer of Pharmaceutical Chemistry, College of Pharmacy, Cairo University, 2000-2004.
*Lecturer of Pharmaceutical Chemistry, College of Pharmacy, Cairo University, since 2004.
*Part-time lecturer of Pharmaceutical Chemistry, College of Pharmacy, Beni-Sweif University, since 2006.
*Supervisor of the NMR laboratory of College of Pharmacy Cairo University since june 2007
- B.Sc. (Pharmacy and Pharmaceutical Sciences, Cairo University, Excellent honor, 1993)
- M.Sc. (Pharmaceutical Chemistry, Cairo University, 2000)
MSc thesis entitled:” Synthesis of certain pyranoquinolines as potential antimicrobial agents”; from which one article was published:
”Synthesis of certain pyranoquinolones as potential antimicrobial agents”
Abou-Shady, H.A., Amin, K.M., Hanna, M.M. and Awadallah, F.M.,
Bull.Fac.Pharm.Cairo Univ. (2003), 41(3), 59-73
- Ph.D. (Pharmaceutical Chemistry, Cairo University, 2004)
PhD thesis entitled: ”Synthesis of some pyranoquinolines and related tetracyclic derivatives as potential antineoplastic agents”; from which two articles were published:
“Synthesis of some pyranoquinoline derivatives with anticipated antineoplastic activity”
Amin, K.M., El-Sayed, N.M., Mohammed, S.R. and Awadallah, F.M.,
Bull.Fac.Pharm. Cairo Univ. (2005), 43(3), 87-94
”Synthesis of some new pyranoquinoline derivatives of potential antineoplastic activity”
Amin, K.M., El-Sayed, N.M., Mohammed, S.R. and Awadallah, F.M.,
Egypt.Pharm.J.(2006), 5(1), 157-173
Positions held: *Demonstrator of Pharmaceutical Chemistry, College of Pharmacy, Cairo University, 1994-2000.
*Assistant lecturer of Pharmaceutical Chemistry, College of Pharmacy, Cairo University, 2000-2004.
*Lecturer of Pharmaceutical Chemistry, College of Pharmacy, Cairo University, since 2004.
*Part-time lecturer of Pharmaceutical Chemistry, College of Pharmacy, Beni-Sweif University, since 2006.
*Supervisor of the NMR laboratory of College of Pharmacy Cairo University since june 2007
Post doctoral publication:
1- “Synthesis of novel lactam derivatives and their evaluation as ligands for the dopamine receptors, leading to a D4-selective ligand.”
Fadi M. Awadallah, Franziska Mϋller, Jochen Lehmann, Ashraf H. Abadi
Bioorg. Med. Chem. 2007, 15, 5811-5818.
1- “Synthesis of novel lactam derivatives and their evaluation as ligands for the dopamine receptors, leading to a D4-selective ligand.”
Fadi M. Awadallah, Franziska Mϋller, Jochen Lehmann, Ashraf H. Abadi
Bioorg. Med. Chem. 2007, 15, 5811-5818.
**This article received the Cairo University award for international publications on 27/10/2008.
2- "Synthesis, pharmacophore modeling, and biological evaluation of novel 5H-thiazolo[3,2-a]pyrimidin-5-one derivatives as 5-HT2A receptor antagonists"
Fadi M. Awadallah
Sci. Pharm. 2008, 76, 415-438.
Teaching activities:
- Participating in teaching the undergraduate Pharmaceutical Chemistry (old curriculum) for fourth year students in College of Pharmacy, Cairo University.
- Participating in teaching the undergraduate Pharmaceutical Chemistry (curriculum 801) for fourth year students in College of Pharmacy, Cairo University.
- Participating in teaching the undergraduate Pharmaceutical Chemistry (curricula 801, 802, 803) for fourth and fifth year students in College of Pharmacy, Beni-Sweif University.
- Participating in teaching postgraduate Pharmaceutical Chemistry students in College of Pharmacy Cairo and Beni-sweif Universities.
- Oral examiner for undergraduate students in Colleges of Pharmacy in a number of Egyptian Universities e.g. Cairo, Beni-Sweif, Ismailia, Ain-Shams, and 6th of October Universities.
- Supervising the summer training of undergraduate students in College of Pharmacy, Cairo University.
- Course coordinator of the ‘Performance Appraisal and Quality Assurance Unit (PAQU)
in department of Medicinal and Pharmaceutical Chemistry (curriculum 801) College of Pharmacy, Cairo University.
Conferences:
- The 2nd Conference of Egyptian Humboldtians, under the theme of "Humboldtians in Natural Sciences and Engeneering", German University in Cairo, September 8-9, 2007.
Teaching activities:
- Participating in teaching the undergraduate Pharmaceutical Chemistry (old curriculum) for fourth year students in College of Pharmacy, Cairo University.
- Participating in teaching the undergraduate Pharmaceutical Chemistry (curriculum 801) for fourth year students in College of Pharmacy, Cairo University.
- Participating in teaching the undergraduate Pharmaceutical Chemistry (curricula 801, 802, 803) for fourth and fifth year students in College of Pharmacy, Beni-Sweif University.
- Participating in teaching postgraduate Pharmaceutical Chemistry students in College of Pharmacy Cairo and Beni-sweif Universities.
- Oral examiner for undergraduate students in Colleges of Pharmacy in a number of Egyptian Universities e.g. Cairo, Beni-Sweif, Ismailia, Ain-Shams, and 6th of October Universities.
- Supervising the summer training of undergraduate students in College of Pharmacy, Cairo University.
- Course coordinator of the ‘Performance Appraisal and Quality Assurance Unit (PAQU)
in department of Medicinal and Pharmaceutical Chemistry (curriculum 801) College of Pharmacy, Cairo University.
Conferences:
- The 2nd Conference of Egyptian Humboldtians, under the theme of "Humboldtians in Natural Sciences and Engeneering", German University in Cairo, September 8-9, 2007.
- The 1st Scientific Conference of Faculty of Pharmacy Cairo University, under the theme of “Pharmacy role in Community Health Promotion”, March 29th 2008.
Dissertation: “Synthesis, Pharmacophore modeling, and Biological Evaluation of Novel 5H-thiazolo[3,2-a]pyrimidin-5-one Derivatives as 5-HT2A Receptor Antagonists”.
Dissertation: “Synthesis, Pharmacophore modeling, and Biological Evaluation of Novel 5H-thiazolo[3,2-a]pyrimidin-5-one Derivatives as 5-HT2A Receptor Antagonists”.
- The 1st International Conference of the Quality Assurance and Accreditation Center Cairo University, under the theme of " Quality and Accreditation, The Present and The Prospective", April 15 2008.
Training courses as part of Faculty and Leadership Development Project (FLDP):
- Methods of scientific research 25-29/3/2006.
- Quality assurance and accreditation 7,8/5/2006.
- E-learning 12-14/2/2007.
- Scientific writing and international publishing 26-29/2/2007.
- Evaluation of teaching 26-28/3/2007.
- New tendencies in teaching 21-23/5/2007.
- Workshop on course and program report 4/6/2007.
Contact information:
College mailing address: Department of Medicinal and Pharmaceutical chemistry, College of Pharmacy, Cairo University, Kasr El-Eini Street 11562, Cairo, Egypt.
Home mailing address: El Rehab city, New Cairo, compound 13, bldg. 9, flat 12, 11841, Helwan, Egypt.
Home: 002-02-26070436
*Mobile: 002-012-3483941
*E-mail: fadi_mae@hotmail.com
*preferred contact methods
Training courses as part of Faculty and Leadership Development Project (FLDP):
- Methods of scientific research 25-29/3/2006.
- Quality assurance and accreditation 7,8/5/2006.
- E-learning 12-14/2/2007.
- Scientific writing and international publishing 26-29/2/2007.
- Evaluation of teaching 26-28/3/2007.
- New tendencies in teaching 21-23/5/2007.
- Workshop on course and program report 4/6/2007.
Contact information:
College mailing address: Department of Medicinal and Pharmaceutical chemistry, College of Pharmacy, Cairo University, Kasr El-Eini Street 11562, Cairo, Egypt.
Home mailing address: El Rehab city, New Cairo, compound 13, bldg. 9, flat 12, 11841, Helwan, Egypt.
Home: 002-02-26070436
*Mobile: 002-012-3483941
*E-mail: fadi_mae@hotmail.com
*preferred contact methods
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