Med Chem Tutoring January 24 By Alaina Darby

Know the objectives… I’m sure you have realized this by now. Some TB drugs are prodrugs that required activation by bacterial enzymes. List up. What is a general stain method for Mtb? Is Mtb Gram-negative or Gram-positive? Mtb survive in host for many years by entering dormancy. Study about non-replicating Mtb. List up the second-line TB drugs. Which one is aminoglycoside? Molecular target of bedaquline Molecular target of ethambutol Structure of delemanide and its mode of action Molecular target of rifampicin Study Crohn’s disease. Are antibiotic effective? What are NOD1 and NOD2? Structure of chloroquine Structure of artesunate. Is it orally bioavailable? Combination chemotherapy for Plasmodium falciparum infections. Mode of action and utility of metronidazole Study about interferons What are causative organisms of sexually transmitted infections (STIs)? Study about HIV/AIDS Nucleoside-based antiviral drugs Antiretroviral drugs used for the treatment of HIV/AIDS . General structures of nucleoside reverse-transcriptase inhibitors and SAR Non-nucleoside reverse transcriptase inhibitor for the treatment of HIV Tamiflu and its mode of action

Some TB drugs are prodrugs that required activation by bacterial enzymes. List up. Which of the following molecules is a prodrug? A. B. C. D. A and C Page 24

Some TB drugs are prodrugs that required activation by bacterial enzymes. List up. Which of the following enzymes is used to activate Pyraziamide? A. Acidic conditions B. Basic condictions C. Fatty acid synthase I D. Pyrazinamidase A

What is a general stain method for Mtb What is a general stain method for Mtb? Is Mtb Gram-negative or Gram-positive? Which of the following would describe the gram stain of Mtb? A. Gram positive B. Gram negative C. Acid fast D. What is a gram stain? C… Lipid rich, high mycolic acid content

Mtb survive in host for many years by entering dormancy Mtb survive in host for many years by entering dormancy. Study about non-replicating Mtb. Which of the following is not true of the Mtb dormant state? A. Rifampin is active against it B. It can survive for many years C. It is not well understood D. It can reactivate later A Slide 9

List up the second-line TB drugs. Which one is aminoglycoside? Which of the following second-line TB drugs is an aminoglycoside? Ethionamide Cycloserine Amikacin Rifampin C

List up the second-line TB drugs. Which one is aminoglycoside? Which of the following second-line TB drugs is an aminoglycoside? A. B. C. D. D What are they? Cipro Ethionamide (also a prodrug!!) Cycloserine Amikacin

Molecular target of bedaquline What is the target of Bedaquiline? Binds to the 30S ribosomal subunit Mycobacterial ATP synthase Mycolic acid in the cell wall DNA-dependent RNA polymerase B What is each of these? Aminoglycosides (or tetracyclines) Bedaquiline Delamanid (new one) Rifampin

Molecular target of ethambutol What is the target of Ethambutol? DNA-dependent RNA synthase Arabinosyl transferase Pyrazinamidase 30S ribosomal subunit B

Structure of delemanide and its mode of action Which of the following is delamanide? A. B. C. D. A Slide 23

Structure of delemanide and its mode of action Which of the following is not true of delemanide? Works against intracellular bacteria in vivo Disrupts the Mtb cell membrane Part of the nitroimidazole class of anti-TB drugs Has not been shown that benefits of it outweigh risks A Slide 23

Molecular target of rifampicin What is the molecular target of rifampicin? α-subunit of DNA-dependent RNA polymerase β-subunit of DNA-dependent RNA polymerase α-subunit of RNA-dependent DNA polymerase β-subunit of RNA-dependent DNA polymerase B

Study Crohn’s disease. Are antibiotic effective? What are NOD1 and NOD2? Which of the following does not describe Crohn’s disease? Occurs only in the large intestine Highest prevalence is in Israel, northern Europe, and North America Causes abdominal pain, diarrhea, vomiting, and weight loss Certain bacteria may be responsible for causing it A

Study Crohn’s disease. Are antibiotic effective? What are NOD1 and NOD2? Which of the following has been assumed to be a causative agent of CD? Mycobacterium avium Mycobacterium kansasii Mycobacterium tuberculosis Mycobacterium gordonae A

Study Crohn’s disease. Are antibiotic effective? What are NOD1 and NOD2? Which of the following describes the mechanism for CD susceptibility? Mutation of the intracellular pattern recognition receptor NOD1 Mutation of the extracellular pattern recognition receptor NOD1 Mutation of the intracellular pattern recognition receptor NOD2 Mutation of the extracellular pattern recognition receptor NOD2 C Know that this receptor is involved in host immune response to bacterial infections (MAP) Also related to IBD!!

Structure of chloroquine Which of the following is chloroquine? A. B. C. D. B Pamaquine Chloroquine Primaquine Bulaquine

Structure of chloroquine What is the highlighted portion of chloroquine called? Quinacrine core Quinine core Quinone core Quinolone core B

Structure of artesunate. Is it orally bioavailable? Which of the following is artesunate? A. C. B. D. A B. RBx11160 C. Artemether D. Arteflene

Structure of artesunate. Is it orally bioavailable? Which of the following is true of artemisin administration? Cannot be giving orally due to GI side effects Is given orally as prophylaxis for malaria Given IV as prophylaxis for malaria Given IV as treatment for severe malaria D

Combination chemotherapy for Plasmodium falciparum infections. Which of the following drugs is used in combination with quinine for prevention against malaria and is especially effective for prophylaxis of the liver stage of Plasmodium? Chloroquine Atovaquone Doxycycline Proganil C Slide 39

Mode of action and utility of metronidazole Which of the following does not describe metronidazole? Can be used to treat aerobic bacterial infections Can be used to treat protozoal infections May cause CNS toxicity Forms a redox active compound A

Study about interferons How are interferons typically administered? IM PO IV SQ A

Study about interferons Which of the following diseases may be prevented with an interferon injection immediately following infection? HIV HCV HPV HAV B… hep C

Study about interferons Which of the following types of interferon has been approved from prophylactic treatment of CMV? Interferon-α Interferon-β Interferon-γ Interferon-δ A

What are causative organisms of sexually transmitted infections (STIs)? Which of the following viral infections can cause an STI? Hepatitis A Hepatitis B Hepatitis C Hepatitis D B

What are causative organisms of sexually transmitted infections (STIs)? Which of the following bacteria causes syphilis? Haemophilus ducreyi Neisseria gonorrhea Lymphogranuloma vereum Treponema pallidum D

What are causative organisms of sexually transmitted infections (STIs)? Which of the following is a protozoal infection that also causes a STI? Chlamydia trachomatis Trichomonas vaginalis Candida albicans Human immunodeficiency virus B

Study about HIV/AIDS Which of the following is not true of HAART? May have severe side effects Compliance is important to prevent resistance May be of benefit to patients with low viral loads There are no risks for patients with low viral loads D

Study about HIV/AIDS Which of the following is true of HIV/AIDS? HIV-1 is more infective than HIV-2 HIV-2 is more infective than HIV-1 HIV-1 and HIV-2 are equally infective Neither HIV-1 and HIV-2 are very infective A

Nucleoside-based antiviral drugs Which of the following is not true of NRTI resistance? Mutations in the N-terminal polymerase domain reduce enzyme affinity to bind the drug Mutations may occur as insertions or deletions in the background Excision enhancement mutations are selected for by thymidine analogs Resistance to one NRTI does not confer resistance to the other NRTIs D Slide 85

Antiretroviral drugs used for the treatment of HIV/AIDS . Which of the following is not included in Atripla? Efavirenz Emtricitabine Zidovudine Tenofovir C

Antiretroviral drugs used for the treatment of HIV/AIDS . Which of the following is not a component of Trizivir? Abacavir Emtricitabine Zidovudine Lamivudine B