Designing Compounds for Next-Gen Antibiotics and Cancer Treatments

Chemists at Cold Spring Harbor Laboratory (CSHL) have generated a novel set of molecular compounds and are evaluating them as possible candidates for novel drug discovery leads. They discovered a number of these molecules that have the potential to be developed into antibiotics and cancer treatments. It is more like simple hard chemistry.

Professor John Moses of CSHL’s lab invented an effective new method of joining molecules to create new compounds. Moses refers to Accelerated SuFEx Click Chemistry (ASCC) as a ground-breaking method. It is one of the most recent developments in the Nobel-winning field of click chemistry, which K. Barry Sharpless, Moses’ mentor, pioneered.

Molecules are quickly snapped together by click chemistry to form intricate new structures. This makes it possible for researchers to gather a large number of compounds for additional study. Click chemistry can produce more compounds with higher yields in fewer steps using Accelerated SuFEx.

If you can make molecules, you can test them. And with this technology, you can make them fast.”

John Moses, Professor, Cold Spring Harbor Laboratory

More than 150 unique new compounds, including derivatives of intricate natural molecules, were produced by Moses and the team using ASCC. Producing and purifying such a variety of molecules could have taken months in the past. In a matter of days, Moses and the group were prepared. Following that, they tested these novel compounds on drug-resistant bacterial strains and cancer cells.

Joshua Homer, a Research Scientist in Moses’ lab, created a variety of compounds in one set of experiments that resembled the anti-cancer drug combretastatin A4. Homer discovered that two of the newly identified molecules have the capability to eliminate cancer cells that commonly exhibit resistance to standard chemotherapy.

These molecules hold the potential to pave the way for effective treatments for challenging-to-treat forms of breast and pancreatic cancers in the future.

The researchers produced molecules that bore similarities to the antibiotic dapsone. They discovered that a few of these compounds worked well against bacteria resistant to dapsone. According to Homer, ASCC might aid chemists in repurposing other sophisticated antibiotics to get past the resistant mechanisms of pathogens.

In the future, Moses and the group will keep using ASCC to hone leads into viable drug candidates and discover new avenues for drug discovery. They anticipate that additional researchers will incorporate Accelerated SuFEx technology into their drug discovery platforms in the interim.

Summing up the advantages of ASCC, Moses says: “It’s just a way to find function. You can always improve things and optimize. But let’s get there as quick as possible. Hopefully, we can accelerate the whole process.”

Cocktails & Chromosomes: Molecules to change the world, with CSHL’s John Moses, Ph.D.

Moses gives a quick primer on click chemistry during a CSHL Cocktails & Chromosomes talk. Stay tuned to the end to see him bring out his mentor, two-time Nobel laureate K. Barry Sharpless. Video Credit: Cold Spring Harbor Laboratory

Source:
Journal reference:

Homer, A., J., et al. (2024) Modular synthesis of functional libraries by accelerated SuFEx click chemistry. Chemical Science. doi.org/10.1039/D3SC05729A

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