What is Medicinal Chemistry (section 3)

 Section 3: Historical Development of Medicinal Chemistry

Medicinal chemistry, like all sciences, has a rich history that dates back thousands of years. The way we make and use medicines today is based on centuries of trial, error, observation, and scientific development. In this section, we will explore how medicinal chemistry evolved from traditional herbal remedies to a modern scientific discipline.

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1. Ancient Civilisations and Herbal Medicines

The earliest form of medicine was based on plants. People in ancient civilisations used herbs, roots, and minerals to treat diseases. This form of healing is called traditional medicine.

a. India – Ayurveda

• Around 3000 BCE, Indian sages documented herbal remedies in the form of Ayurveda.
• Texts like the Charaka Samhita and Sushruta Samhita describe over 700 medicinal plants.
• Some Ayurvedic formulations are still used today.

b. China – Traditional Chinese Medicine (TCM)

• Similar to Ayurveda, TCM uses herbs, acupuncture, and body balancing.
• Ginseng, ginger, and green tea are examples.

c. Egypt and Mesopotamia

• The Ebers Papyrus (Egypt, 1550 BCE) lists hundreds of plant-based treatments.
• Mesopotamians used clay tablets to record recipes and healing practices.

These early healers did not understand molecules or chemistry, but they knew which plants helped and which ones harmed.

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2. The Greco-Arab Period and the Concept of Active Ingredients

a. Hippocrates and Galen (Greece)

• Hippocrates (460–370 BCE) is called the "Father of Medicine".
• He introduced the idea that diseases have natural causes, not supernatural ones.
• Galen (129–216 CE) created compound formulations, now known as galenicals.

 

b. Arab Influence – Alchemy to Chemistry

• Arab scholars translated Greek works and added their own knowledge.
• They introduced distillation and extraction techniques.
• Avicenna (Ibn Sina) wrote The Canon of Medicine, influencing medicine for centuries.
• Alchemy gave rise to modern chemistry.

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3. The Birth of Modern Chemistry and Isolation of Drugs

a. Paracelsus (1493–1541)

• A Swiss physician who said: “All substances are poisons; the right dose differentiates a poison and a remedy.”
• He introduced the concept of using chemicals as medicines.
• Rejected traditional theories and supported the idea of dosage and chemical purity.

b. Isolation of Active Principles

• Early 1800s: Scientists began isolating pure compounds from plants.
• These pure compounds were the active ingredients responsible for medicinal effects.

Examples:

• 1804: Morphine from opium (Friedrich Sertürner)
• 1817: Emetine from ipecacuanha
• 1820: Quinine from cinchona bark (used to treat malaria)
• 1831: Atropine from belladonna

This was the beginning of phytochemistry — the chemistry of plant-based compounds.

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4. The Rise of Organic Chemistry and Synthetic Drugs

In the 19th century, organic chemistry developed rapidly. Scientists learned to make organic molecules in the laboratory.

a. First Synthetic Drug – Chloral Hydrate (1869)

• Used as a sedative.

b. Aspirin (1897)

• Synthesised by Felix Hoffmann (Bayer) from salicylic acid.
• It became the world’s first widely used synthetic drug.

c. Sulfa Drugs (1930s)

• First effective antibacterial drugs.
• Prontosil, discovered by Gerhard Domagk, saved millions of lives.

Synthetic drugs were easier to produce in large quantities and more stable than plant extracts.

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5. The Antibiotic Revolution

One of the biggest breakthroughs in medicinal chemistry came with the discovery of antibiotics.

a. Penicillin (1928)

• Discovered by Alexander Fleming from the mould Penicillium notatum.
• Mass-produced during World War II and saved countless soldiers from infections.

b. Streptomycin (1944)

• Discovered by Selman Waksman from soil bacteria.
• Effective against tuberculosis.

Antibiotics opened a new era of infection control and inspired the search for more microbial products.

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6. Hormones, Vitamins, and Steroids

In the early 20th century, scientists isolated and synthesised important biological molecules:

• Insulin (1921): For diabetes treatment
• Thyroxine: For thyroid disorders
• Vitamin C (ascorbic acid): Synthesised in 1933
• Cortisone: A steroid used in inflammation

These molecules were now produced synthetically or semi-synthetically, making them accessible to millions.

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7. Development of Rational Drug Design

Until now, many drugs were discovered by chance. But with better understanding of biology and chemistry, a rational approach was developed.

a. Receptor Theory

• Proposed in the early 1900s, it suggested that drugs work by binding to specific receptors in the body.

b. Structure–Activity Relationship (SAR)

• Chemists modified structures and studied how these changes affected activity.
• Example: Improving sulfa drugs for better activity and fewer side effects.

c. Beta Blockers, ACE Inhibitors

• Drugs for heart disease designed with the knowledge of biological targets.

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8. The Biotechnology and Molecular Biology Era (1980s–2000s)

Advances in biology transformed drug discovery.

• Recombinant DNA technology: Enabled production of insulin, growth hormone.
• Monoclonal antibodies: For cancer and autoimmune diseases.
• Targeted therapy: Specific drugs for specific genes or proteins (e.g., imatinib for leukemia).
• PCR and genomics: Helped in understanding genetic diseases.

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9. 21st Century – Genomics, AI, and Precision Medicine

In the current era, medicinal chemistry is integrated with:

• Artificial Intelligence (AI): Helps predict drug behaviour and screen compounds.
• Big Data and Machine Learning: Analyse millions of molecules quickly.
• CRISPR and Gene Editing: For gene-level treatment.
• Personalised/Precision Medicine: Drugs tailored to individual genetic profiles.
• Computer-Assisted Drug Design (CADD): Saves time and cost in drug development.

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Summary Table: Timeline of Major Milestones

Period	Development
3000 BCE	Herbal medicines in India, China, Egypt
400 BCE	Hippocrates promotes natural cause of diseases
1000 CE	Avicenna writes Canon of Medicine
1800s	Isolation of morphine, quinine, etc.
1897	Synthesis of aspirin
1928	Discovery of penicillin
1930s	Sulfa drugs introduced
1950s–60s	Hormones, steroids, and vitamins synthesised
1970s–80s	Rational drug design, receptor theory
1990s–2000s	Biotechnology and genetic drugs
2010s onwards	AI, genomics, and personalised medicine

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Conclusion

The development of medicinal chemistry has moved from simple plant remedies to sophisticated, targeted therapies. This journey reflects how scientific thinking, technological tools, and patient needs have guided the evolution of medicine. Understanding this history gives students a deeper respect for the field and helps them become thoughtful and innovative future pharmacists and researchers.