Breaking News
February 22, 2019 - Successful testing of multi-organ “human-on-a-chip” could replace animals as test subjects
February 22, 2019 - Analysis of cervical precancer shows decline in two strains of HPV
February 22, 2019 - Sugary stent eases suturing of blood vessels
February 22, 2019 - From surgery to psychiatry: A medical student reevaluates his motivations
February 22, 2019 - Is New App From Feds Your Answer To Navigating Medicare Coverage? Yes And No
February 22, 2019 - New pacemakers powered by heartbeats could reduce need for surgery
February 22, 2019 - The United States records highest drug overdose death rates
February 22, 2019 - Phase 1 data reinforce safety profile of new drug for treating Duchenne muscular dystrophy
February 22, 2019 - Vitamin D supplementation less effective in the presence of obesity, shows study
February 22, 2019 - Sarepta Announces FDA Acceptance of Golodirsen (SRP-4053) New Drug Application for Patients with Duchenne Muscular Dystrophy Amenable to Skipping Exon 53
February 22, 2019 - An institutional effort to reduce the amount of opioids prescribed following lumbar surgery
February 22, 2019 - Failure to take statins leads to higher mortality rates | News Center
February 22, 2019 - New study explains why some patients report phantom sensations after limb amputation
February 22, 2019 - First motor-controlled heart valves implanted by Mainz University Medical Center
February 22, 2019 - Novel preclinical model mimics persistent interneuron loss seen in preterm infants
February 22, 2019 - Global health burden of glaucoma has increased, study reveals
February 22, 2019 - A holistic approach key to minimize treatment complexity in patients with interstitial lung disease
February 22, 2019 - 1 in 10 middle-aged Chinese adults are at high risk for heart disease, finds study
February 22, 2019 - More than half a million breast cancer patient’s lives saved by improvements in treatment
February 22, 2019 - Study finds no evidence that tougher policies prevent teenage cannabis use
February 22, 2019 - New blood test detects genetic disorders in fetuses
February 22, 2019 - Lower Self-Perception Observed in Children With Amblyopia
February 22, 2019 - Up to 15 percent of children have sleep apnea, yet 90 percent go undiagnosed
February 22, 2019 - Rare pulmonary defect prompts parents’ nationwide search for answers | News Center
February 22, 2019 - Lesbian and bisexual women at greater risk of being overweight, study finds
February 22, 2019 - UQ research may explain why vitamin D is essential for brain health
February 22, 2019 - Heart Attacks Rising Among Younger Women
February 22, 2019 - How your smartphone is affecting your relationship
February 22, 2019 - Orthopaedic surgeon receives prestigious award, $10 million grant | News Center
February 22, 2019 - New sepsis test could save thousands of lives
February 22, 2019 - Cervical cancer could be eradicated by 2100
February 21, 2019 - Sustained smoking cessation can lower risk of seropositive RA
February 21, 2019 - Thousands with chronic UTIs are not receiving the treatment they need
February 21, 2019 - Are teens getting high on social media? The surprising study seeking the pot-Instagram link
February 21, 2019 - Stanford expands biobank services | News Center
February 21, 2019 - Scientists identify link between drinking contexts and early onset intoxication among adolescents
February 21, 2019 - Strong social support may reduce cardiovascular disease risk in postmenopausal women
February 21, 2019 - Rapid expansion of interventions could prevent up to 13 million cases of cervical cancer within 50 years
February 21, 2019 - Motif Bio Receives Complete Response Letter From The FDA
February 21, 2019 - Researchers map previously unknown disease in children
February 21, 2019 - A skeptical look at popular diets: Going gluten-free
February 21, 2019 - Podcast: KHN’s ‘What The Health?’ How Safe Are Your Supplements?
February 21, 2019 - Factors associated with increased risk of developing surgical site infections
February 21, 2019 - Anticipatory signals in eye movements can help measure attentive capacity, learning with greater precision
February 21, 2019 - Study explores daily exposure to indoor air pollutants
February 21, 2019 - Evening exercise does not negatively affect sleep, may also reduce hunger
February 21, 2019 - Artificial intelligence technique can be used to identify alcohol misuse in trauma setting
February 21, 2019 - Overweight, obesity in adolescence associated with increased risk of renal cancer later in life
February 21, 2019 - BGU develops new AI platform for monitoring and predicting ALS progression
February 21, 2019 - Researchers discover a new promising target to improve HIV vaccines
February 21, 2019 - Brief Anesthesia in Infancy Does Not Mar Neurodevelopment
February 21, 2019 - Gaming system helps with autism diagnosis
February 21, 2019 - Heart Disease: Six Things Women Should Know
February 21, 2019 - More States Say Doctors Must Offer Overdose Reversal Drug Along With Opioids
February 21, 2019 - Researchers explore case studies focused on industries that kill more people than employed
February 21, 2019 - Only half of GP practice buildings are fit for purpose
February 21, 2019 - Intense exercise, fasting and hormones can enhance waste-protein removal, study shows
February 21, 2019 - Scientists can monitor brain activity to predict epileptic seizures few minutes in advance
February 21, 2019 - Study quantifies hepatic and intestinal mRNA expression of Ugt isoforms in rats
February 21, 2019 - ‘Apple-Shaped’ Body? ‘Pear-Shaped’? Your Genes May Tell
February 21, 2019 - Can we repair the brain? The promise of stem cell technologies for treating Parkinson’s disease
February 21, 2019 - Trump Plan To Beat HIV Hits Rough Road In Rural America
February 21, 2019 - PENTAX Medical introduces new electrosurgical and argon plasma coagulation platforms
February 21, 2019 - Trump plan to beat HIV hits rough road in rural America
February 21, 2019 - Eating blueberries every day could help decrease blood pressure
February 21, 2019 - ‘No Second Chances’ report calls for new measures to combat cardiovascular disease in Australia
February 21, 2019 - Mayo clinic researchers discuss local case studies of leprosy
February 21, 2019 - Scientists demonstrate key role of salt in allergic immune reactions
February 21, 2019 - Experts propose revising the criteria for diagnosis of Parkinson’s disease
February 21, 2019 - The med student and the machine
February 21, 2019 - Hey, Hey! Ho, Ho! Is Striking For School Nurses The Way To Go?
February 21, 2019 - Latest research encourages children to move out and learn through physical activity
February 21, 2019 - Proper oral hygiene and regular visits to dentist can promote heart health
February 21, 2019 - New, versatile technique for remote control of transplanted cells in Parkinson’s
February 21, 2019 - Why melanoma tumors in the brain may be worse?
February 21, 2019 - New project aims to improve lung disease care in Appalachia
February 21, 2019 - Drug increases melanin production in some people with albinism
February 21, 2019 - Over 1 in 3 adults miss the mark on protein, finds study
February 21, 2019 - CymaBay Therapeutics Announces Seladelpar Granted Breakthrough Therapy Designation by the FDA for the Treatment of Primary Biliary Cholangitis
February 21, 2019 - A correlation between obesity and income has only developed in the past 30 years
Researchers harness visible light to develop safer building block for drug discovery

Researchers harness visible light to develop safer building block for drug discovery

image_pdfDownload PDFimage_print

When you reach for a bottle of acetaminophen, you may be looking for relief from a headache. But if you take more than what is recommended, the drug can damage your liver.

That’s because when a component of the drug–a substructure referred to as an aniline–breaks down in the liver, it can produce toxic metabolites. Now, University of Michigan researchers have developed a new building block that can serve as a safer alternative for the development of new medicines.

The pharmaceutical industry commonly uses anilines as the basis for developing new drug therapies. But the way the liver metabolizes many drug therapies containing anilines can cause toxic side effects. For example, overloading the liver with acetaminophen can cause liver failure. Other drugs can trigger a harmful immune response in the body as a result of the unwanted metabolism.

“Aniline is a common structure that’s easy to make,” said Corey Stephenson, U-M professor of chemistry. “The problem with anilines is that they are readily metabolized by our liver, and that can create problems. We want our drugs to be metabolized, but not in a way that causes them to have toxic effects.”

Stephenson and his team’s research into developing a safer building block began as a desire to explore ways to use visible light to drive chemical reactions. The team began looking into structures called aminocyclopropanes, hoping to convert them into more complex and more valuable compounds.

The team recognized the potential to convert aminocyclopropanes into a different compound, a 1-aminonorbornane, which is more complex and traditionally very difficult to synthesize. The research team also realized that these 1-aminonorbornanes could be highly useful in discovering new drug leads.

The benefit? 1-Aminonorbornanes don’t seem to be metabolized in harmful ways by liver enzymes.

“We realized that we can use these aminonorbornane cores as a substitute for an aniline,” said Daryl Staveness, a U-M postdoctoral researcher and American Cancer Society fellow. “Usually, drug companies will need to re-engineer drugs that use it to avoid that oxidation event. But in using aminonorbornanes, we don’t have to worry about those metabolic processing issues.”

The process the team used to convert aminocyclopropanes into the beneficial 1-aminonorbornane structures has another benefit: because the reaction needed to produce the molecule is powered by visible light, 1-aminonorbornanes can be produced cheaply, sustainably and on a large scale.

“It’s inexpensive. It’s mild,” said co-author and U-M graduate student Taylor Sodano. “Using traditional chemical approaches, 1-aminonorbornanes have been previously difficult to synthesize, requiring inefficient sequences of reactions and forcing inflexible conditions. Now, we can do it in one step at room temperature, using visible light and environmentally friendly conditions.”

To produce 1-aminonorbornanes, the team employed a photocatalyst to execute the desired transformation. Catalysts are compounds that facilitate a chemical reaction, and in the case of photoredox catalysis, the special brand of photochemistry the team used, the catalysts operate by using the energy of visible light to shuttle electrons between molecules.

When Sodano and Staveness mix their photocatalyst with an aminocyclopropane and expose the solution to LED lights, the catalyst takes an electron from the aminocyclopropane, initiating the process that produces the 1-aminonorbornane, which is still missing its electron. The catalyst then gives the electron back to complete the reaction. Nothing else needs to be added other than the light, making this process exceptionally environmentally benign.

Study co-author Klarissa Jackson of Lipscomb University studied the safety of the 1-aminonorbornanes. She applied the compounds to liver fragments containing the enzymes that typically metabolize drug compounds. She found that when the enzymes broke down the 1-aminonorbornanes, the process did not produce the harmful metabolites that result from anilines.

“People are always striving to generate safer and better medicines, and what we need from a chemistry standpoint are more tools to do that,” Stephenson said. “Additionally, we can combine sustainability with these new tools, so you get both an environmentally friendly way to produce these compounds, and the final products have the potential to have implications in human health.”

Tagged with:

About author

Related Articles