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Future

In Their Quest For Cures, Medical Researchers Take Cues From Mother Nature

Scientists are looking at nature’s myriad molecules -- studying substances like tree bark and fungi -- in hopes of coming up with cures for cancer and other maladies.

Yew tree bark contains an anti-tumor agent
Yew tree bark contains an anti-tumor agent
Cédric Duval

Always a source of scientific inspiration, Mother Nature is now playing a key role in combinatorial chemistry, explained researchers involved in last week's "Chemistry and Health: from molecules to medicines' conference, hosted by France's Université Paris-Sud. An important line of study in the pharmaceutical industry, combinatorial chemistry involves rapid synthesis or the computer simulation of a large number of different but structurally related molecules or materials.

Two decades ago, combinatorial chemistry caught the imagination of researchers. "Back then, we thought that we could rapidly create a library of several thousand molecules, but that idea was too simplistic so it did not work," says Fanny Roussin of France's National Center for Scientific Research (CNRS). "What we must do is combine several approaches including the study of natural substances, which has already proved its worth."

A study published earlier this year in The Journal of Natural Products confirms that natural molecules, also called "bio-sourced" molecules, have made a phenomenal contribution to human health. From 1981 to 2006, about 50% of new molecules have been extracted from plants, fungus and microorganisms. For instance, almost 60% of anti-tumor agents are extracted from nature. Perhaps the best example is Taxotere, a blockbuster drug marketed worldwide by Sanofi-Aventis. Taxotere is in fact an analogue of taxol which is an extract from the bark of yew trees.

"Studying natural substances makes us discover complex and original molecules that we haven't thought of before," says Roussi. Her research took her to Malaysia, a country that has rich endemic biodiversity. Several plant extracts have already been taken there. The screening of those plant extracts has led to the identification of a new compound called Meiogynine A, isolated from the bark of Meiogyne cylindrocarpa, and capable of restoring apoptosis. This process of programmed cell death that may occur in multi-cellular organisms is inhibited in more than 50% of cancers, resulting in the uncontrolled growth of tumors. Meiogynine A acts on some anti-apoptotic proteins and might have the ability to restart the process of programmed cell death. Bio-sourced molecules are also interesting because of their unique active modes.

For instance, the discovery of a fungal toxin called Brefeldin A (BFA) foresees new ways to inhibit G proteins. "In many diseases including cancer, the role of these proteins has been recognized for a long time, but inhibiting them causes potentially dangerous side-effects because G proteins communicate signals from many hormones and neurotransmitters," says Mahel Zeghouf, a CNRS researcher at the Laboratory of Structural Enzymology and Biochemistry.

Even if researchers are interested in natural molecules, it is still very difficult to put them to use medically. Most of the time, they cannot be found everywhere, and the quantity of active agents that can be extracted from them is too small. The natural places where they grow are also fragile. For instance, the Meiogyne cylindrocarpa forest in Malaysia was destroyed to make room for oil palm plantations. Synthesis can be helpful in that case because it allows researchers to produce larger, exploitable quantities. "The problem is that it is difficult to synthesize these molecules (or analogues) quickly and at a reasonable price," says Laurent Schio, a medical manager in medicinal chemistry and oncology at Sanofi.

One solution is hemisynthesis. A relatively simple natural molecule biologically close to the active principle, which can be found quite easily, has to be identified. Then, "missing parts' are introduced by chemical means. Meiogynine A and analogues were created like this, because other more traditional methods had failed," says Roussi.

Read the original article in French.

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Geopolitics

Senegal's Democratic Unrest And The Ghosts Of French Colonialism

The violence that erupted following the sentencing of opposition politician Ousmane Sonko to two years in prison left 16 people dead and 500 arrested. This reveals deep fractures in Senegalese democracy that has traces to France's colonial past.

Image of Senegalese ​Protesters celebrating Sonko being set free by the court, March 2021

Protesters celebrate Sonko being set free by the court, March 2021

Pierre Haski

-Analysis-

PARIS — For a long time, Senegal had the glowing image of one of Africa's rare democracies. The reality was more complicated than that, even in the days of the poet-president Léopold Sedar Senghor, who also had his dark side.

But for years, the country has been moving down what Senegalese intellectual Felwine Sarr describes as the "gentle slope of... the weakening and corrosion of the gains of Senegalese democracy."

This has been demonstrated once again over the last few days, with a wave of violence that has left 16 people dead, 500 arrested, the internet censored, and a tense situation with troubling consequences. The trigger? The sentencing last Thursday of opposition politician Ousmane Sonko to two years in prison, which could exclude him from the 2024 presidential elections.

Young people took to the streets when the verdict was announced, accusing the justice system of having become a political tool. Ousmane Sonko had been accused of rape but was convicted of "corruption of youth," a change that rendered the decision incomprehensible.

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