mch02final - ‘ Medicinal Chemistry 311 Name 2333;...

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Unformatted text preview: ‘ Medicinal Chemistry 311 Name 2333; B‘Nfi'g‘fihmg) 1 December 16, 2002 Final Examination Student No. 30:) (ESHE Use a No. 2 pencil. Write your name on the top of this exam and on the front and back of the bubble sheet. Use your 8-digit person number (as ID No.) followed by a blank 5 ace 9th on back of the bubble sheet. DO NOT USE YOUR SOC. SEC. NUMBER! Fill in bubble sense where applicable. For the multiple choice questions, select the one right answer. For each question, the correct answer is worth 2 points, unless otherwise indicated. Read each question carefully. Double-check all your answers! if you change an answer, be certain to erase the original answer completely. 1. Which of the following statements regarding the therapeutic index (TI) is correct? 3 Ti = EDsolLDso 1-05; lie. go Ti = LDsolEDso 0 Ti = therapeutic dose/toxic dose nom'ucoee l MYQQQDXVL bum d) Tl = minimum effective doselmaximum tolerated dose mu<muIm lb‘wimum 9) TI = ’ i ted ' ' e 2. Wi'iich of the following mechanisms is unlikely to lead to antibiotic resistance? a) increased cellular efflux of the drug cry-o b) decreased affinity of the target to the drug tats c) increased enzymatic degradation of the drugtgs increased cellular uptake of the drug —ua.:fi\é M3 Edie;wa cents“ V'me e) decreased metabolic activation of the drug 39 3. Which of the following mechanisms is responsible for isoniazid resistance? _ I _ I ‘< we.— (M‘so-I‘OJM'LGMUE newest: a) methylation of an adenine In ribosomal RNA has wmxxacsalcmmgt b change in peptidoglycan precursor structure vmgnHLQN defect in the catalaselperoxidase enzyme system d) active TET-pump MWVM. e) mutated porinsvtlttccau;N 4. Modification of drug structure by acet iation and hos ho Iation plays a role in the bacterial resistance against which of the following antibiotics? ._____.____________ a tetracyclines L1 as — Qofim‘o\ aminoglycosides ehmom1 a: H c) B-lactams d) quinolones e) macrotidr 5. Which of the following antibiotics is NOTworking by inhibition of ba_ct_e_ij§il_pr_gt_ein biosynthesis? M a) streptomycin as b) erythromycin sci-J EQWGNC‘C c) tetracycline Babs seesaw - chloramphenicol 5J1»: m ‘e vancomycin a-rmuzsL-é‘ \c; w.“ kauo {cs-.1 mXHL‘M'B 6. Which of the following statements about antibiotic resistance is not correct? a) spontaneous mutations can lead to drug resistance acct: b) many resistant mutants are less viabie than their sensitive wild type cots c plasmids can carry different resistance genes we — resistance genes cannot be transferred between different bacterial strains e) non—pathogenic bacteria can carry drug resistance genes to“) 7. Withdrawal of a drug removes the selective pressure that causes the shift of a bacterial population from a drug sensitive to a drug resistant one and helps fighting the spread of drug resistance. is this statement TRUE or FALSE? 8. AH but one of the following statements are correct about the antibiotic vancomycin; a) it inhibits bacterial growth b) it binds to the substrate of peptidoglycan transpeptidase at is an inhibitor of bacterial cell wall synthesis can 't is an aminogiycoside e) it is a giycopeptidefii 9. When alanine racemase is added to a 1:1 mixture of L-alanine and D-alanine, which of the following will happen? 6650 so '. so a) all L-alanine will be converted to D-alanine Nc- b) 50% of L-alanine wili be converted to D-alanine c) 25% L-alanine will be converted to D-aianine d) 50% of D-alanine will be converted to L-aianine @ no change 10. B-Lactam antibiotics are selectively toxic, because they bind to a target essential for bacteria that is not present in mammalian cells. Is this statement TRUE or FALSE? TRUE ) FALSE 11. All but one of the following can be said about the participation of pyridoxal phosphate in the alanine racemase reaction: ‘13; CHO 9 P OH O/lxo / 90 e I N. N CH; H @ it is the ccfactor form of vitamin B2 b) it serves as a cofactor for the racemase c) it forms a Schiff—base with the amino acid substrate d) its Schiff—base with the product undergoes hydrolysis 9} it acts as an electron sink 12. D—cycloserine inhibits 2 sequential reactions (racemase and synthetase), which blocks the pathway more effectively, than if it inhibited either one alone. If the drug inhibited the reaction A to B 60%, and inhibited the reaction B to C 75%, what would be the yield of product C? The yield of C in the absence of the drug is assumed to be 100%. ‘ The yield of product 0 is: “9% a 5% “‘5‘ if; 10% if“? L44, 0) 15% 43/ to d) 20% e) 25% 13. D—Cycloserine can cause toxic side effects, due to its ability to deplete pyridoxal phosphate in mammalian cells. The administration of which one of the following vitamins can prevent the toxic side effects of D-cycloserine? a) vitamin B1 b) vitamin B; c) vitamin Ba @ vitamin 85 e) vitamin B12 14. Prontosil is a prodrug that requires metabolic activation to form which one of the following drugs: a) D-cycloserine b) cyprofloxacin atui'mcmu e. c cephalosporin sulfanilamide e) streptomycinrvo 15. All but one of the following results from conversion of chioramphenicol to its I palmitate prodrug form: ‘ 0 OZN‘Q‘Ki/‘O JL(CH2)HCH3 OH HN CHci2 TI’ 0 3) decreases the water solubility of the parent drugcfifi b) masks the bitterness of the parent drug $5, 0) makes the parent drug more palatable 06w @ decreases the lipid solubility of the parent drugé- e) increases the lipid solubility of the parent drug 16. Chemical instability of the penicillin molecule is due to which of the following structural components? 0 NH 8 CH3 Mich O . "602:4 _ a) the thiazolidine ring the B-Iactam ring.-w:€~‘n'u\ QM M**“%“"“r‘ “L‘M‘LS c the acylside-chain d) the carboxyl group e) the gem-methyl groups 17. How many chiral centers are in the cephalosporin molecule: RYNH S O .- COzH a) 1 b) 2 c) 3(- d) 4 e) 5 '18. AH but one of the following statements regarding the action of penicillin is correct: a) the inhibition of its target enzyme involves a suicide mechanism b) the inhibition of its target enzyme is irreversible Us”? GD an active site cysteine residue is covalently modified mommsou: d) the opening of the beta-lactam relieves the strain of the 4—membered ring fits e) it forms an analog of the acyl enzyme intermediate of the normal reaction ME c, ‘19. Which of the following is the molecular target of action of penicillin? a D-ala—D-ala Gimme an we peptidoglycan transpeptidase c) the terminal dipeptide of the peptidoglycan precursor wmm‘a-w d) B-lactamase ' ' ' ’ fink— Munch: e) penicilltnase7‘5‘r‘) it“ 20. What component of the bacterial cell is targeted by cephaiosporins? 1 \r a) 30 S ribosomal subunit “NW-Liaise 95W”? ‘6 93*“‘"L¥‘\-'~‘5 b) 50 S ribosomal subunit fitfih‘oflt‘t cm 0) ribosomal RNA d messenger RNA Le); ell wall 21. S-Aminopenicillanic acid, a starting material for the production of semi—synthetic penicillins is obtained by hydrolysis of naturally occurring penicillins with the aid of which of the following enzymes? 3) . .H. b) transpeptidase c racemase it penicillin acylase 'eg-iaetemase 22. Augmentin is a mixture of clavulanic acid and which of the following drugs? ampicillin mew-J amoxicillin c) cloxaciliin d) oxacillin e) methiciliin 23. Which of the following statements is (WWW? @it is a suicide substrate of B~iactamase «w» ) . . . . . itfimmmmwmhmnpfladamm ) it lacks antibiotic activity “Mel oect (one: we” Sam:\ c d) it is hydrolyzed by B-Iactamase 2) its structure lacks the B-lactam ring 24. Which of the following is not shared by peptidoglycan transpeptidase and B— Iactamase, when they interact with penicillin? a) the B—lactam ring of the drug is split open hair“ b) the drug serves as a substrate \n c) a penicilloyl enzyme intermediate is formed tats, d; a serine residue becomes acylated can. am ater can serve as a second substrate armkwal mow, for Mflbrckfigifi 25. All but one of the following contribute to the selective ' ' ’ 1 a) they target a unique enzyme present in bacteria only 46:: s b) they inhibit bacterial cell wall biosynthesis was @ they have a six-membered ring fused with the B—Iactam ring they irreversibly inactivate peptidogiycan transpeptidase e) mammalian cells do not have cell walls vats 27. In vancomycin resistance a critical H-bond cannot be made between the drug and its target, due to the replacement of D-alanine with which of the following? 8) haul-same b) L-serine 0’65“ c) D-serine fl _ _ -. L-lactate 0 Lu)“ cfiILmdme 27. All but one of the following rings belong to the structure of ciprofloxacin: o ptvugiifl " a) benzene??? pyridine c piperazine d) piperidine e) cyclopropyl 28. What is the target of ciprofloxacin? a) DNA polymerase b RNA polymerase @DNA gyrase peptidoglycan transpeptidase @144Jt.{\\\' o e) alanine racemase hittaoflcme 29. Members of the penicillin family of drugs that bind well to B-lactamase always become hydrolyzed faster than those that bind poorly. Is this statement TRUE or FALSE? _ —c.\\ use. osmumfl‘stb 0300:") Won}.ng a TRUE -\o..$\- out” mks. 3Qro adgE—chJr-eg ALSE '30. Monobactams that are inhibitors of peptidogiycan transpeptidase are efficiently hydrolyzed by B-lactamase. Is this statement TRUE or FALSE? a TRUE ALSE 31. Acyclovir (acycloguanosine) undergoes metabolic activation to the triphosphate form, which involves initial phosphorylation to the monophosphate by one of the following enzymes. which is encoded by the virus: 0 O O N N HN HN N N OP HzN “N N [/ckl— Led—owe a) deoxyguanosine kinase b) guanosine kinase @thymidine kinase thymidylate kinase e) thymidylate synthase 32. Ali but one of the following is a factor in the selective toxicity of acyclovir: a) metabolic activation to the monophosphate occurs in virally infected cells ~35 b) metabolic activation to the monophosphate cannot be catalyzed by cellular enzymes varh-‘Oi'rui. Exhauin c) acyclovir incorporated into viral DNA is not removed by repair enzymes {@the herpes viral DNA polymerase is less sensitive to inhibition by acyclovir triphosphate than the host cell DNA polymerase e) conversion of acyclovir monophosphate to the triphosphate is can be carried out only by virally encoded kinases can; 33. Which of the following structural feature is primarily responsible for the action of acyclovir at the molecular level? a? the lack—loe—ZLGH—gm the lack of the 3'-OH groupc— e‘kux'qumx'Nabn'uN our.»er c the lack of the—550mm d) the acyclic nature of acycloguanosine e) the difference between the structure of thymidine and acycloguanosine 34. The mechanism of action of acyclovir involves all but one of the following: a) inhibition of viral DNA synthesis b DNA chain termination inhibition of virai RNA synthesis d) inibition of herpes virus DNA polymerase e) inhibition of viral DNA chain elongation 35. HIV reverse transcriptase is capable of transcribing both RNA to DNA and DNA to DNA. Is this statement TRUE or FALSE? TRUE FALSE 36. The life-cycle of the human immunodeficiency virus (HIV) provides many selective targets for drug action, but the currently approved anti-AIDS drug target only two viral processes. AH but one of the following are additional targets for new drug development: a HIV integrase khaki transcription of the integrated viral DNA into viral RNA c) uncoating of the virus after cellular entry sou; d) assembly of viral particles “2+9 e) recognition of the virus by cell surface receptors the; 37. AZT (Zidovudine) is the first drug approved by the FDA for the treatment of AIDS caused by HIV. AZT is the closest structural analog of which of the following nucleosides? thymidine - deo ytidine c) de y anosine d) adenosine e) uridine 38. Which of the following statements about AZT is False? a) its metabolic activation is carried out by cellular enzymesiflzs b) it is a prodrug «5“; c) it is phosphorylated in the cell to the 5’-triphosphate~b¢ ‘3 d its 3'-OH group is replaced by an azido group was qé) it is more selectively toxic than acyclovir 39. The mechanism of action of AZT involves at! but one of the following: a) incorporation into the newly synthesized viral DNA to) inhibition of reverse transcriptase c) inhibition of viral DNA chain elongation d DNA chain termination @) inhibition of the integration of viral DNAflinto the host chromosomal DNA iCflNH-bo i—KCH LE?)- 40. All but one of the following enzyme activities are encoded by the HIV genome: RNA polymerase b) reverse transcriptase mm n tram am A C) integrase "to-tho keen (XUUMu‘a-cmfl. d) aspartate protease margarita m e) RNASe H 'kacvnw 'I‘sN A 41. All but one of the following result from the lack of fidelity of reverse transcriptase: a) high rate of mutations v69 b) failure of vaccine development “b” gDrapid emergence of drug resistance V3“ \ repair of incorporation mistakes {emu \s-Lrw Mt” e) need for drug combinations in the therapy of AIDS was “mama—‘15“ 42. What is the substrate for the RNAse H activity of HIV reverse transcriptase? the RNA component of viral RNA-DNA hybrids RN“ “‘5 H “‘3‘3‘°‘*“" “M ‘FN c DNA copies of the genomic viral RNA in am; “NA “gm-b d) viral—DNA-DM-‘my’brrdr 9) viral messenger RNAs aé single stranded genomic viral RNA 43. Drug resistance against some HIV reverse transcriptase inhibitors. like AZT, may render the virus sensitive to other members of the same family of drugs. like 3TC that the virus was previously resistant to. Is this statement TRUE or FALSE? TRUE ) FALSE 44. Which of the following drugs is used to treat HIV positive pregnant women in Africa to prevent infection of the newborn? @indinavir 1) ) nevirapine c) 3T0 d) AZT e) ddC 45. AZT-resistant HIV strains, once become resistant to 3T0 during combination therapy of AIDS, may become sensitive to AZT again. Is this statement TRUE or FALSE? @9) TRUE it, ) FALSE 46. HIV protease inhibitors i terfere with which of the following stages of the viral a) attachment b) reverse transcription c) integration d ribosomal synthesis of viral proteins @viral protein processing 'fi \ 47. HIV protease inhibitors were designed as transition state analog inhibitors of the i- enzyme, which is an aspartate protease. Which moiety of indinavir (below) is the ' transition state mimic? / N 0" ’t \N K, i o HN/"\‘o a) the pyridine ring b the amide on the piperazine ring the amide next to the benzyi side-chain d) the 2°-alco with the (S)-configuration e) the 2°-alcl_ o with the (Ri-configuration H 48. The antiherpes drug 5-iodo-2’—deoxyuridine is isosteric with which of the . 9 A a) 2‘-deoxyadenosine b) 2'-deoxyguanosine @2‘—deoxycytidine d) thymidine e) 2'-deoxyinosine 49. 5-iodo-2’-deoxyuridine (lDU) can only be used as a topical antiviral agent, due to which the following? a) poor water solubility b poor lipid solubility § systemic toxicity poor bioavailabilty e) rapid metabolism 50. Most cancers can be caused by which of the following? a) chemical carcinogenstgw b) UV light $5255 c) viruses Ugh-G: d spontaneous mutationscg 9 Q): of the above 51. Cancer patients treated with S-MP may develop hyperurecemia, due to degradation of nucleic acid purines, and to formation of thiouric acid from S-MP @TRUE b) FALSE 10 52. About half of all cancers have a missing or defective p53 gene. which is involved in the cellular response to DNA damage. if DNA damage is beyond repair, which process is initiated in a normal cell by the functional p53 protein? a) DNA replication b) cell division c) mitosis d necrosis (:5). programmed cell death mitoses, 53. Wtion occurs in which phase of the cell cycle? a) Go [3 G1 x... d) (32 @M Ce“ bl‘i\'$\‘q N 54. Which one of the following anticancer drugs act specifically during the S phase of the cell cycle? a) 5-fiuorouracil b) vjncaffifioids taxol inkl‘mvs (“Genie ) tamoxifen e) cyclophosphamide 55. Which one of the following anticancer drugs does noiundergo metabolic activation? a) 5-fluorouracil we b 6-mercaptopurinedsu taxol d) methotrexate e) cyclophosphamide 56. S-Fluorouracil (5—FU) is the drug of choice in the treatment of most gastro- intestinal maiignancies. in the cell, it is converted to its active form, 5-fluoro—2’- deoxyuridine 5’-phosphate (FdUMP), which is a mechanism-based inactivator of which enzyme? 0 J55» HN l H a thymidine kinase hvmidylate synthase 0) DNA polymerase d) dihydrofoiate reductase e) aromatase 11 66. Inhibition of estrogen biosynthesis or blocking the estrogen receptor are two of the rational approaches to the treatment of estrogen dependent breast cancer. RUE b) FALSE 6?. The biosynthesis of estradiol from testosterone is carried out by the enzyme aromatase. which involves oxidative removal of the 19—CH3-group, which involves all but one of the following: 13 12 OH OH to on?” es trad iol testosterone a) conversion of CH3 to CH20H b) conversion of CH20H to CHO 0 conversion of CHO to HCOOH conversion of CHO to 002 G e) aromatization of the A-ring was; 68. 19-Nor-19-propenyl following statements i sterone is an inhibitor of aromatase. Which of the garding this inhibitor? .1 H O 19-nor-19-propenyl testosterone a) it is a mechanism-based inhibitor 573:5 b) it serves as a suicide substrate for aromatase ~32. c) it is an irreversible inhibitorngeh d the propenyl group is oxidized by the enzyme to an eiectrophilic group @the propenyl group is oxidativeiy removed by the enzyme 69. Which of the following drugs is an estrogen rece tor antagonist? a) Finasteride (Proscar) 1;:va b) p-Aminoglutethimide c) Anastrazoie (Arimidex) @ Tamoxiphen (Nolvadex) e) Paclitaxel 14 70. Strong binding of drugs to serum albumin may result in adverse drug interactions. The administration of drugZ may affect drug1 in all but one of the | following ways: a) increase of the unbound fraction of drug‘l decrease of the bound fraction of drug1 @symptoms of drug1 overdose é lack of the pharmacological effects of drug1 e) increased rate of elimination of drug1 71. Most drug incompatibilities are due to chemical reactions between the drug and its environment (or another drug) that takes place after administration. is this statement TRUE or FALSE? RUE b FALSE T2. All but one of the following drugs are incompatible with penicillin: a) aminoglycosides b) streptomycin c) gentamycin @ captopril e) tetracycline 73. Tetracycline should not be taken with all but one of the following: a) milky; ‘ ‘ f : N b) milk ofmagnesia We CWVM‘: «:1 mm lam‘xm if) 0] calcium fortified orange juice Lee-5 d antacids of unknown composition e525 club soda 74. When drug2 induces metabolizing enzymes that degrade drug1, then the dose of drugl must be Is this statement TRUE or FALSE? \‘N C‘— a TRUE FALSE 75. Which of the following is attributed to Woods and Fildes? a) therapeutic index b discovery of penicillin é isolation of pure penicillin? d) discovery of sulfanilamide e) antimetabolite theory 15 1. 2. 3. 4. 5. 6. 7. 8. 9 @G'GG'U'CLQQU'WW'DQWG-GUOGU‘ 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. mmmmc-mac-mnc-c-naonauc-Q 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. gonacnmnmaanggoucacg 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. manurggaQNc-nmnm ...
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This note was uploaded on 12/16/2009 for the course MCH 311 taught by Professor Kalman during the Spring '08 term at SUNY Buffalo.

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mch02final - ‘ Medicinal Chemistry 311 Name 2333;...

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