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13 Central University of Rajasthan Department of Pharmacy School of Chemical Sciences & Pharmacy M. Pharm. (Pharmaceutical & Medicinal Chemistry) Third In-Semester Examination Subject: Medicinal Chemistry-II (MPMC-202) Date: April 24, 2013 Max. Marks: 20 Answer all the questions Q.1 What is the difference between slow, tight binding enzyme inhibitors and enzyme inactivators. Explain the enzyme inactivators in details with examples. [4] Q.2 Explain the type of inhibition of enzyme E observed in following condition [2] The structure of enzyme inhibitor is similar to the structure of product P Q.3 The following drug acts through type of enzyme inhibition. Explain. [2] Q.4 What do you mean by drug resistance? Write the mechanisms through which the drug resistance is observed. [2] Q.5 Differentiate between killed and attenuated vaccine. Which vaccine is used to boost the humoral immunity? [2] Q.6 What are the third generation vaccines? What are the advantages and disadvantages of these vaccines against the pharmaceutical drugs? [2] Q.7 Give the full form of the RISC and briefly explains its biochemical nature and role in Antisense- RNA mediate gene silencing. [2] Q.8 Highlight how exogenous introduction and establishment of dsrna in to a cell completely silences the expression of the corresponding gene. [2] Or Q.8 With appropriate schematic diagram, describe the procedure of the gene silencing via Antisense- RNA or initiating with mirna molecules. [2] Q.9 Briefly explain the phenomenon of co-suppression observed by Napoli and compare it with the RNA interference reported by A. Fire and C. Mello. [2] Or Q.9 Highlight the role of following in the Antisense-RNA/RNAi mediated gene silencing: [2] i. sirna ii. DICER iii. RNA- dependent RNA Polymerase iv. RNA exonucleases

14 Central University of Rajasthan Department of Pharmacy, School of Chemical Sciences & Pharmacy M. Pharm. (Pharmaceutical & Medicinal Chemistry) Third In-Semester-II Examination Subject: Drug Metabolism (MPMC-221) Date: April 23, 2013 Max. Marks: 20 Answer all the questions Q.1 Explain the advanced drug metabolism prediction tool based on QSAR/pharmacophore based approaches. [4] Q.2 Write a short note on METEOR - a rule based drug metabolism prediction tool. [4] Q.3 Which liver-based in vitro drug metabolism technology is used for study of following metabolic profile? Explain the same in details. [6] (i) Soluble phase II enzyme-glutathione S-transferase (ii) CYP and UGT Q.4 Write the types of cell lines used to study drug metabolic profile along with advantages & disadvantages of each. [4] Q.5 Explain the use of target based methods in drug metabolism with example [2]

15 Max. Marks: 20 CENTRAL UNIVERSITY OF RAJASTHAN Department of Pharmacy School of Chemical Sciences & Pharmacy M. Pharm. (Pharmaceutical & Medicinal Chemistry) Third In-Semester-II Examination (April 22, 2013) Basic in Molecular Biology (MPMC-210) Time: 1hr Note: All Questions are compulsory. Each question carry equal marks (2 marks each). Q1: What is the difference between transformation and recombinant selection? Describe with suitable example. Q2. During self splicing a lariat contains a closed loop and a linear end. An Intron has the following sequence: 5 -GUPuAGUA-60 nucleotide-uacuuaucc-100 nucleotides- PY 12 NPyAG-3. Which sequence would be found within the closed loop of the lariat? Q3. A eukaryotic pre-mrna contains 5 exons and 4 introns in a sequence order i.e. 5 - exon1-intron1-exon2-intron2-exon3-intron3-exon4-intron4-exon5-3. During the splicing mechanism, which snrnps will remain associated with intron after the lariat formation? a) U2,U1&U5 snrnps b) U2,U4&U6 snrnps c) U1,U4&U6 snrnps d) U2,U5&U6 snrnps Q4. During the initiation of translation in prokaryotes the first amino acid will bind at which position of ribosome and trna? a) A site of the 30s rrna and 5 end of trna b) P site of the 30s rrna and 5 end of trna c) P site of the 30s rrna and 3 end of trna d) A site of the 30s rrna and 3 end of trna Q5. A polypeptide chain has a sequence of amino acid B1 to B10. During the elongation stage which amino acid will be at the top of the growing polypeptide and which factors (prokaryotes and eukaryotes both) are involved in the translocation mechanism of the growing polypeptide? At which position of the polypeptide chain the new amino acid joined. Q6. How the newly synthesized mrna is protected from degradation by the exonuclease enzymes activity in eukaryotes? Explain your answer in brief. Q7. Write a brief note on each of the following with reference to their involvement in the Plant Tissue Culture Procedure : A. Explant B. Apical Meristem C. Callus Q8. Briefly describe the composition of Plant Tissue Culture medium and highlight the role of growth hormones (Cytokinin and Auxin). Q9. Enlist and explain different steps involved in a standard Plant Tissue Culture Procedure. Q10. Enlist some of the important advantages Micropropagation over Naturalpropagation.

16 Central University of Rajasthan Department of Pharmacy, School of Chemical Sciences & Pharmacy M. Pharm. (Pharmaceutical & Medicinal Chemistry) Third In-Semester-II Examination Subject: Rational Drug Design (MPMC-223) Date: April 22, 2013 Max. Marks: 20 Answer all the questions Q.1 Explain with reasons, the five main problems associated with protein structures from PDB database to be used for protein-ligand docking. Write how to address them. [5] Q.2 Explain different types of scoring function used in molecular docking. Write details about Glide scoring function. [5] Q.3 The fragment connection method in de novo design involves the connection of well placed fragments via linkers. Explain the precaution to be taken for selection of linkers with suitable example. [2] Q.4 Explain the major disadvantage of sequential build up methods in de novo design with example. [2] Q.5 What is site point? Explain site-point connection method in brief with suitable example [3] Q.6 What do you mean by pose in molecular docking? Explain the procedure/method to obtain the same. [4]

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23 Central University of Rajasthan School of Chemical Sciences & Pharmacy, Department of Pharmacy M. Pharm. (Pharmaceutical & Medicinal Chemistry) End of Semester-II Examination (May 17, 2013) Paper: MPMC-202 (Medicinal Chemistry-II) Max. Marks: 50 Time: 3 hrs Part A All questions are compulsory. Each Question carries 3 marks. Q.1 (i) What do you mean by saturation of the enzyme. (ii) Describe with (a) α-helices (b) β- turns (c Psi (ψ) and Phi (φ) angle Q.2 Discuss various techniques employed for amino acid analysis with proper mechanism. Compare their various advantages and disadvantages Q.3 The structure of enzyme inhibitor is similar to the structure of substrate but there is no effect of substrate concentration on the reversal of inhibition. Explain Q.4 Define generic drugs. What are their advantage/disadvantages over biologics Q.5 What are the recombinant DNA vaccines? Give the suitable example and their response to immunity Q.6 Explain mechanism of Edman degradation using Trp-His-Leu tripeptide as an example? Describe advantages and disadvantages of it for peptide structure determination. PART B Attempt any FIVE questions. Each Question carries 4 marks. Q. 7 With suitable diagrammatic representation describe the role of the following in Antisense mediated gene silencing: i. Argnote protein ii. RISC (RNA induced silencing complex) iii. Dicer iv. SiRNA, MiRNA Q.8 With suitable diagrammatic representation, describe how exogenous introduction of small amount of dsrna ensures comprehensive and ever-lasting Antisense mediated gene silencing Q.9 With appropriate diagrammatic representation, explain in detail the molecular mechanism of dsrna and mirna mediated RNA interference. Explain each step involved in the process Page 1 of 2

24 Q.10 Define & explain in brief the following i) Primary structure (ii) Tertiary structure (iii) Quaternary structure (iv) Ramachandran plot Q.11 Wheather transition state analogs as enzyme inhibitors and slow, tight binding enzyme inhibitors are similar? Explain? Q.12 What do you mean by drug resistance? Write the mechanisms through which the drug resistance is observed PART C Answer any one of the following questions (Q. No. 13 or 14). Q.13 (i) Draw structure for the following peptides: [3M] (a) Val-Leu-lIe-Thr-NH 2 (b) His-Arg-Lys-Orn-Asn-Glu (c) Arg- Trp-Orn-Pro-NH 2. (ii) What are the peptidomimetics, explain with the following examples [6M] (a) TRH (b) CCK (iii) Explain the type of enzyme inhibition observed in the following reaction [3M] H N NH2 CYP N NH CYP Q.14 (i) Derive the Michaelis-Menten equation and its Lineweaver-Burk form [3M] (ii)write the structures of peptides A, B & C in the following reaction [6M] N 2 (iii) Explain the suicide substares using following example [3M] Page 2 of 2

25 Central University of Rajasthan School of Chemical Sciences & Pharmacy, Department of Pharmacy M. Pharm. (Pharmaceutical & Medicinal Chemistry) End of Semester-II Examination (May 15, 2013) Paper: MPMC-221 (Drug Metabolism) Max. Marks: 50 Time: 3hrs Part A All questions are compulsory. Each Question carries 3 marks. Q.1 The uricosuric agent probenecid has not been reported to undergo any aromatic hydroxylation. Explain with justification. Q.2 Propose the aromatic hydroxylation product of timidazole, an antiprotozoal drug Q.3 (i) Phenols predominantly undergo O-glucuonidation as compared to O-sulfation. Explain with reason. (ii) Mercapturic acid derivatives results from which phase II metabolism reactions. (iii) Explain the importance of human drug biotransformations. Q.4 Explain the mechanism of following reaction Q.5 Write the major Phase-II metabolite of following drug molecule. Q.6 In silico methods to predict biotransformation are classified as Local & Global methods. Write the difference between these methods and explain any one global method in brief. Page 1 of 3

26 PART B Attempt any FIVE questions. Each Question carries 4 marks. Q. 7 Write the metabolite B (which is further converted into carcinogenic metabolite) formed in the following reaction and explain the mechanism for the same. Q.8 Explain in details the substrate specificity of Human CYP enzymes (decision tree for Human CYP substrates). Q.9 Write a short note on Glutathione conjugation. Explain all the possible mechanisms with suitable examples. Q.10 List down the stratergies used for reduction of CYP inhibition and explain in brief all of them with suitable examples. Q.11 Name the most vulnerable site of metabolism in the following molecules and explain any one strategy to achieve metabolic stability (i) (ii) Q.12 Explain in detail the catalytic cycle of FMO. Page 2 of 3

27 PART C Answer any one of the following questions (Q. No. 13 or 14). Q.13 (i) Which liver-based in vitro drug metabolism technologies would be used for (A) Isolation of metabolites &(B) Study of drug-drug interaction. Explain in details with proper justification [6M] (ii) The structure of enalapril (ACE inhibitor used to treat hypertension) is shown below. Write two major phase I metabolites of enalapril which could be conjugated in Phase II metabolism pathway. Write the names of catalyzing enzyme. [6M] COOH N O NH O Q.14 (i) Explain the catalytic mechanism of CYP450 enzyme with particular attention to O the iron-oxygen containing intermediates. [8M] (ii) The reactive quinoid system could be detoxified by direct reaction with GSH. Write the mechanism in detail. [4M] Page 3 of 3

28 Central University of Rajasthan School of Chemical Sciences & Pharmacy, Department of Pharmacy M. Pharm. (Pharmaceutical & Medicinal Chemistry) End of Semester-II Examination (May 20, 2013) Paper: MPMC-223 (Rational Drug Design) Max. Marks: 50 Time: 3hrs Part A All questions are compulsory. Each Question carries 3 marks. Q.1 Write detailed explanation of term Pharmacophore. (Do not write just definition.) Q.2 Write true or false No minimization method can guarantee the location of the global energy minimum. Explain your answer with proper justification. Q.3 What do you mean by Potential energy surface. Explain various terms associated with it. Q.4 What is the advantage of de novo design method? What are the problems in de novo design and how to address those problems? Write in brief. Q.5 Explain briefly how to validate newly generated pharmacophore models. Q.6 Write at least six important assumptions used in 3D-QSAR methods. PART B Attempt any FIVE questions. Each Question carries 4 marks. Q. 7 Forecast the best suitable computational method which could be used in following condition to design new molecules. Give proper justification. (i) X-ray crystal structure of an enzyme with PDB code 1U6S was reported with substrate. There are no reported inhibitors for the same enzyme. (ii) A large number of molecules including active, inactive and moderate active are reported as histamine H 3 receptor antagonist and no X-ray crystal structure of receptor is available. Q.8 Explain the advantages of connection methods over whole molecule method in de novo design. Explain how to select the proper linkers in fragment connection method. Page 1 of 2

29 Q.9 What is force field parameterization? Explain its importance and write a short note on how it is done. Q.10 What is conformation of a molecule. Explain briefly various simulation based conformational search methods used in molecular mechanics. Q.11 Systematic search explores the conformational possibilities by making regular and predictable changes to the conformation. Explain Q.12 What is the difference between bonded and non-bonded interactions in force field? Explain various non-bonded terms included in force field in brief. PART C Answer any one of the following questions (Q. No. 13 or 14). Q.13 (i) Explain the following with reference to 3D-QSAR methods (a) Alignment of molecules [2M] (b) Calculation of molecular interaction energy fields [3M] (c) Model generation and validation [2M] (ii) Explain the various terms included in Glide empirical scoring function [5M] Q.14 (i) Docking is used to predict in where and in which relative orientation a ligand binds to a protein which is referred to as the. Explain in details the procedure/method to obtain the same. [5M] (ii) The pharmacophore does not represent a real molecule or a real association of functional groups, but a purely abstract concept that accounts for the common molecular interaction capacities of a group of compounds towards their target structure. Explain [7M] Page 2 of 2