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.

Photo – Neosnaps

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Iran-Saudi Arabia Rivalry May Be Set To Ease, Or Get Much Worse

The Saudis may be awaiting the outcome of Iran's nuclear talks with the West, to see whether Tehran will moderate its regional policies, or lash out like never before.

Military parade in Tehran, Iran, on Oct. 3


LONDON — The Iranian Foreign Ministry spokesman Saeed Khatibzadeh said earlier this month that Iranian and Saudi negotiators had so far had four rounds of "continuous" talks, though both sides had agreed to keep them private. The talks are to ease fraught relations between Iran's radical Shia regime and the Saudi kingdom, a key Western ally in the Middle East.

Iran's Foreign Minister Hossein Amirabdollahian has said that the talks were going in the right direction, while an Iranian trade official was recently hopeful these might even allow trade opportunities for Iranian businessmen in Saudi Arabia. As the broadcaster France 24 observed separately, it will take more than positive signals to heal a five-year-rift and decades of mutual suspicions.

Agence France-Presse news agency, meanwhile, has cited an unnamed French diplomat as saying that Saudi Arabia wants to end its costly discord with Tehran. The sides may already have agreed to reopen consular offices. For Saudi Arabia, the costs include its war on Iran-backed Houthis rebels fighting an UN-recognized government in next-door Yemen.

The role of the nuclear pact

Bilateral relations were severed in January 2016, after regime militiamen stormed the Saudi embassy in Tehran. Amirabdollahian was then the deputy foreign minister for Arab affairs. In 2019, he told the website Iranian Diplomacy that Saudi Arabia had taken measures vis-a-vis Iran's nuclear pact with the world powers.

It's unlikely Ali Khamenei will tolerate the Saudi kingdom's rising power in the region.

He said "the Saudis' insane conduct toward [the pact] led them to conclude that they must prevent [its implementation] in a peaceful environment ... I think the Saudis are quite deluded, and their delusion consists in thinking that Trump is an opportunity for them to place themselves on the path of conflict with the Islamic Republic while relying on Trump." He meant the administration led by the U.S. President Donald J.Trump, which was hostile to Iran's regime. This, he said, "is not how we view Saudi Arabia. I think Yemen should have been a big lesson for the Saudis."

The minister was effectively admitting the Houthis were the Islamic Republic's tool for getting back at Saudi Arabia.

Yet in the past two years, both sides have taken steps to improve relations, without firm results as yet. Nor is the situation likely to change this time.

Photo of Iranian Supreme Leader Ali Khamenei in 2020

Iranian Supreme Leader Ali Khamenei in 2020


Riyadh's warming relations with Israel

Iran's former ambassador in Lebanon, Ahmad Dastmalchian, told the ILNA news agency in Tehran that Saudi Arabia is doing Israel's bidding in the region, and has "entrusted its national security, and life and death to Tel Aviv." Riyadh, he said, had been financing a good many "security and political projects in the region," or acting as a "logistical supplier."

The United States, said Dastmalchian, has "in turn tried to provide intelligence and security backing, while Israel has simply followed its own interests in all this."

Furthermore, it seems unlikely Iran's Supreme Leader Ali Khamenei will tolerate, even in this weak period of his leadership, the kingdom's rising power in the region and beyond, and especially its financial clout. He is usually disparaging when he speaks of Riyadh's princely rulers. In 2017, he compared them to "dairy cows," saying, "the idiots think that by giving money and aid, they can attract the goodwill of Islam's enemies."

Iranian regime officials are hopeful of moving toward better diplomatic ties and a reopening of embassies. Yet the balance of power between the sides began to change in Riyadh's favor years ago. For the kingdom's power has shifted from relying mostly on arms, to economic and political clout. The countries might have had peaceful relations before in considerably quieter, and more equitable, conditions than today's acute clash of interests.

If nuclear talks break down, Iran's regime may become more aggressive.

Beyond this, the Abraham Accord or reconciliation of Arab states and Israel has been possible thanks to the green light that the Saudis gave their regional partners, and it is a considerable political and ideological defeat for the Islamic Republic.

Assuming all Houthis follow Tehran's instructions — and they may not — improved ties may curb attacks on Saudi interests and aid its economy. Tehran will also benefit from no longer having to support them. Unlike Iran's regime, the Saudis are not pressed for cash or resources and could even offer the Houthis a better deal. Presently, they may consider it more convenient to keep the softer approach toward Tehran.

For if nuclear talks with the West break down, Iran's regime may become more aggressive, and as experience has shown, tensions often prompt a renewal of missile or drone attacks on the Saudis, on tankers and on foreign shipping. Riyadh must have a way of keeping the Tehran regime quiet, in a distinctly unquiet time.

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