Malaria and Quinine Quiz

Medicinal Chemistry Introduction

• CH456 Medicinal Chemistry course, 2025, by James H. Gerlach

The Five Deadliest Infectious Diseases

• Rabies: essentially 100% case fatality rate
• Ebola hemorrhagic fever: 83% case fatality rate
• Marburg hemorrhagic fever: 80% case fatality rate
• H5N1 avian influenza: ~60% case fatality rate
• Nipah virus: 40% to 70% case fatality rate

Share of Total Disease Burden by Cause, World 2021

• Measured in Disability-Adjusted Life Years (DALYs)
• DALYs account for both years of life lost and years lived with disability
• One DALY equals one lost year of healthy life
• Cardiovascular diseases account for a significant portion of the total burden

Share of Total Disease Burden by Cause, Canada 2021

• Cardiovascular diseases, cancers, and musculoskeletal disorders are major contributors to the total burden of disease

Disease Burden from Communicable, Maternal, Neonatal and Nutritional Diseases, World

• Estimated disease burden in Disability-Adjusted Life Years (DALYs) per year.
• Data shows trends over time, with different diseases contributing more or less over the years

Disease Burden from Communicable, Maternal, Neonatal and Nutritional Diseases, Canada

• Estimated disease burden in Disability-Adjusted Life Years (DALYs) per year.
• Shows trends over time, with different diseases contributing differently over the years

Deaths from Infectious Diseases, 1980 to 2021, World

• Estimated annual death toll from HIV/AIDS, diarrhea, malaria, respiratory, and other infectious diseases.
• Overall trend is downward since 1980

Deaths from Infectious Diseases, 1980 to 2021, Canada

• Estimated annual death toll from HIV/AIDS, diarrhea, malaria, respiratory, and other infectious diseases.
• Overall trend is upward since 1980

Global Trends in Estimated Number of TB Deaths and Mortality Rate, 2000-2020

• Data presented in a graphical format showing trends in TB deaths and mortality rates.
• Includes total TB, HIV-negative, and HIV-positive breakdowns.

The Deadliest and Most Communicable Diseases

• Chart visualising various diseases based on case fatality rate and basic reproduction number (Ro)
• Infectious diseases are categorized based on primary transmission method and their mortality rate

Malaria is the Disease Responsible Historically for the Most Worldwide Deaths

• Malaria is a life-threatening disease caused by parasites.
• Transmission occurs through infected female Anopheles mosquitoes.
• Preventable and curable, with estimated 263 million cases and 597,000 deaths in 2023.
• WHO African Region carries a disproportionate share of the global malaria burden.
• Children under 5 are significantly affected (76% of deaths in the Region in 2023).

Countries with Indigenous Cases of Malaria in 2000 and Their Status by 2023

• Detailed map visualization of malaria cases in different countries

Quinine

• Cinchona bark contains quinine (anti-malarial) and quinidine (anti-arrhythmic) alkaloids.
• The first European cured of malaria fever, possibly, was the wife of the Spanish Viceroy of Peru.
• In 1753, the Peruvian bark was named Cinchona after the countess.

Homeopathy and Cinchona

• Homeopathy's origins are connected to Cinchona bark testing.
• Samuel Hahnemann, founder of homeopathy, felt symptoms from an overdose of Peruvian bark.

Discovery of the Malaria Parasite

• Alphonse Laveran, a French military doctor, discovered a motile parasite in infected patients' blood in Algeria in 1878.
• He was awarded a Nobel Prize in 1907.

Quinine Properties

• Natural white crystalline alkaloid
• Antimalarial, analgesic, antipyretic and anti-inflammatory properties
• Bitter taste, used in gin and tonic

Quinine Total Synthesis

• Hundreds of years of efforts to synthesize quinine.
• Various chemists and researchers discovered methods and processes to isolate and synthesize quinine over time

Woodward-Doering Quinine Synthesis

• Detailed account of different chemist's approaches to achieve quinine total synthesis.
• Discussion on experimental challenges

Stork Stereoselective Quinine Synthesis

• Different steps involved in achieving synthesis

Related Antimalarial Drugs

• Chloroquine (1934) and Amodiaquine (1948) are related antimalarial drugs.
• Chemical structures are presented and years of development are noted

Paracetamol (Acetaminophen)

• IUPAC name: N-(4-hydroxyphenyl)-acetamide
• Other chemical names: N-acetyl-para-aminophenol, APAP, para-acetamidophenol
• International Nonproprietary Name (INN): Paracetamol

What's the origin of these names?

• Different names for paracetamol are presented and details on their origins

Julius Axelrod and Bernard Brodie Demonstrated Acetanilide is Metabolized to Paracetamol in 1948

• Acetanilide, initially used for pain and fever.
• Methaemoglobinemia, formed by this drug was a serious side effect, leading to liver and kidney damage.
• Later research demonstrated that the body metabolized acetanilide to paracetamol.

Paracetamol Total Synthesis

• Detailed description of steps in synthesizing paracetamol
• Starting materials and chemical reactions

Paracetamol Mechanism of Action

• Paracetamol acts via cyclooxygenase (COX) pathways and inhibits COX-3 enzyme.
• Metabolised to AM404 and this may impact pain receptors.

Paracetamol Metabolism

• Metabolised primarily through the liver.
• Major metabolites are inactive and excreted in the urine.
• NAPQI is a toxic metabolite and can damage the liver if not quickly detoxified.

Reactions Involved in Paracetamol Metabolism

• Paracetamol is metabolized through reactions like glucuronidation and sulfation reactions.

NAPQI Toxicity

• The toxic metabolite causing liver injury in paracetamol overdose.
• Involved in covalent binding with proteins and nucleic acids.
• Causes cellular and organism responses, leading to necrosis and liver injury.

Treating Paracetamol Overdoses

• Toxic doses range from 4–15g.
• Treatment includes administering acetylcysteine within 8 hours to replenish liver glutathione.
• Without treatment, liver failure can occur.

Test your knowledge on the critical aspects of malaria, its transmission, and the medicinal history of quinine. This quiz explores historical facts, significant figures, and the properties of quinine related to malaria treatment. Challenge yourself and learn more about infectious diseases and their impact.