The work also has implications to accelerate the development of medications

The crystallization process is essential for drug development, petrochemical processing and other industrial actions, but scientists say they are still learning about the complex interactions involved in the construction and dissolution of crystals.

Researchers from the University of Houston and the Free University of Brussels reported in the magazine. Nature For the first time they have demonstrated at the molecular level what happens when two compounds that are known to inhibit the growth of crystals are combined, in this case, antimalarial drugs. The results were unexpected.

“It is expected that the use of two drugs that attacked crystallization in two different ways was synergistic, or at least additive,” said Jeffrey Rimer, professor of Chemical and Biomolecular Engineering Abraham E. Dukler at UH and co-author of the article. . “Instead, we discovered that they can work against each other.”

Working against each other, known as antagonistic cooperation, meant that drugs were actually less effective as a whole than individually. Peter Vekilov, John and Rebecca Moores Professor of Chemical and Biomolecular and Chemical Engineering at UH and another co-author, said the work will allow the design of more effective treatments for malaria, a mosquito-borne disease that killed 435,000 people in 2017, the Most of them children in Africa.

But more generally, it suggests a new way to detect molecules for their potential in drug development, allowing new treatments to be developed more quickly.

“When you are using modifiers, a small change in the structure of the molecule can dramatically alter its performance,” Rimer said.

Malaria is caused by a parasite, which consumes hemoglobin and leaves a compound known as hematin, which the parasite sequesters inside a crystal. Antimalarial treatments work by inhibiting the growth of crystals, releasing hematine to attack the parasite.

For this work, the researchers studied the growth of hematine crystals in the presence of four antimalarial drugs: chloroquine, quinine, mefloquine and amodiaquine, which work in one of two different ways.

Both computationally and experimentally, even through the use of atomic force microscopy, the researchers demonstrated how the compounds that attack crystallization behave by two different mechanisms when combined. The understanding at the molecular level resulting from that behavior suggests a new mechanism for materials science, Vekilov said.

“This mechanism can provide guidance in the search for combinations of suitable inhibitors to control the crystallization of pathological, biomimetic and synthetic materials,” the researchers wrote. “In a broader context, our results highlight the modifying interactions mediated by dynamics and structures in the crystal interface as a major element of the regulation of the shapes and patterns of crystalline structures in nature and industry.”

In addition to Vekilov and Rimer, researchers involved in the project include UH Ph.D. Wenchuan Ma student and collaborator Dr. James Lutsko of the Université libre de Bruxelles.

Source of the story:

Materials provided by Houston university. Original written by Jeannie Kever. Note: The content can be edited by style and length.


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