Medicinal Chemistry

Urgent need to study medicinal plants

1. To rescue knowledge in imminent danger of being lost

Inventory by WHO found 20,000 plant species in use for medicine in 90 countries

Only 250 of those species are commonly used or have been checked for main active chemical compounds

Urgent need to study medicinal plants

2. The utility of plants in current therapy

There has been a rush to develop synthetic medicines based on plant medicines, but often the synthetic medicines don’t work as well as the original plant medicines.

For example – quinine and malaria

Efficacy of Quinine

• Quinine is traditional and effective preventative of malaria

• Synthetic preventatives such as chloroquine, maloprim, and fansidar have largely replaced the use of quinine

• Many strains of Plasmodium have developed resistances to the synthetics and the synthetics are more toxic. It is recommended that people do not take fansidar for more than 3 months due to potential liver damage.

Malaria Cycle

Anopheles freeborni mosquito – intermediate host and vector for Plasmodium sp.

Historical distribution of Malaria

Red areas show countries with malaria today

One of the sources of Quinine – Cinchona succirubra

Cinchona pubescens

Timeline of Quinine Use

• 1633, a Jesuit priest named Father Calancha described how to use quinine bark to cure fevers

• 1645 Father Bartolome Tafur took some bark to Rome and many of the clergy used it

• Cardinal John de Lugo wrote a pamphlet to be distributed with the bark - use of the bark became so widespread that in the papal conclave of 1655 no one died of malaria

• 1654 – English aware of use of quinine bark• 1735, a French botanist named Joseph de Jussieu

journeyed to South America and found and described the tree that is the source of the bark - he sent samples to Sweden where in 1739, Carl Linneaus named the tree genus Cinchona

Timeline of Quinine Use• 20 to 40 species of Cinchona - the species are very

hard to tell apart and the species will hybridize, so the exact number of species is unknown – mostly understorey trees

• 1820 the French chemists Joseph Pelletier and Joseph Caventou isolated the alkaloid quinine from the bark and identified it was the active ingredient in Peruvian bark

• 1861, an Australian named Charles Ledger obtained seeds from an Aymara Indian named Manuel Incra

• by 1930, the Dutch orchards in Java produced 22 million pounds of quinine, 97% of the world’s market

Chemical structure of quinine

Properties of Quinine

• Quinine itself is an odorless white powder with an extremely bitter taste

• It can be used to treat cardiac arrhythmias as well as malaria - it is also used as a flavoring agent

• Quinine prevents malaria by suppressing reproduction of the Plasmodium and also helps prevent some of the fevers and pain associated with malaria

Quinine fluoresces under UV light

Raymond Fosberg in the field in 1948

Cinchona bark drying in the sun in Ecuador, 1944

Urgent need to study medicinal plants

3. To find new molecular models in plants

Many times we can take a plant chemical and modify it or make synthetic copies of it that are very valuable to us.

Lippia dulcis – sweetener from Pre-Columbian America

Lippia as a sweetener

• In Pre-Columbian America, several plants of the genus Lippia were used as sweeteners. (F. Verbenaceae – the verbenas).

• In the 20th century, L. dulcis was chemically analyzed and a new sweetener was found, hernandulcin, that is 800 to 1000 times sweeter than sucrose.

Urgent need to study medicinal plants

4. The wide use of plants in folk medicine

One positive aspect of the use of medicinal plants is their low cost compared to the high price of new synthetic drugs that are totally inaccessible to the vast majority of the world’s people. Another benefit is that most medicinal plants don’t have the kinds of harmful side effects seen with synthetic drugs.

Plants and Human Cosmologies

Cosmologies

Cosmologies are branches of philosophy which deal with the origins and structures of the universe - religions that explain how the universe formed and our place within it are one kind (a very powerful kind) of cosmology

The Oak of Guernica

Basque coat of arms with Oak of Guernica

Oak of Guernica by Wordsworth - 1810

• THE OAK OF GUERNICA

The ancient oak of Guernica, says Laborde in his account of Biscay, is a most venerable natural monument. Ferdinand and Isabella, in the year 1476, after hearing mass in the church of Santa Maria de la Antigua, repaired to this tree, under which they swore to the Biscayans to maintain their "fueros" (privileges). What other interest belongs to it in the minds of this people will appear from the following.

SUPPOSED ADDRESS TO THE SAME

OAK of Guernica! Tree of holier power Than that which in Dodona did enshrine (So faith too fondly deemed) a voice divine Heard from the depths of its aerial bower-- How canst thou flourish at this blighting hour? What hope, what joy can sunshine bring to thee, Or the soft breezes from the Atlantic sea, The dews of morn, or April's tender shower? Stroke merciful and welcome would that be Which should extend thy branches on the ground, If never more within their shady round Those lofty-minded Lawgivers shall meet, Peasant and lord, in their appointed seat, Guardians of Biscay's ancient liberty.

Guernica by Picasso

The Fall by Michelangelo – detail from ceiling of the Sistine Chapel

Moses and The Burning Bush

The sacred Maori Waka Huia

The sacred Maori Waka Huia

Miro tree – Podocarpus ferruginea