In 2010, 21, 089 deaths in the US involved opioid use. By 2022, however, opioid use was involved in 81,806 deaths. While effective for relieving pain, opioid use carries undesirable side effects such as addiction and respiratory depression. Research is thus underway to discover and develop safer alternatives for pain relief.
In the current study, researchers screened a chemical database of over 40,000 substances. In particular, they searched for a substance that would bind to opioid receptors and hold properties required of a pharmaceutical drug, such as being somewhat water-soluble. The top 100 candidates were further assessed through a computational technique known as molecular docking. The resulting top 10 then underwent biochemical analysis in the lab.
In the lab, the researchers exposed human kidney cells to high concentrations of each substance to see whether they would have a toxic effect on the cells or even kill them. They next conducted tests to see whether the substances would bind to pain receptors and influence their function. Ultimately, one compound passed all the tests: aniquinazolin B, found in the marine fungus Aspergillus nidulans.
"The results of our investigations indicate that this substance may have effects similar to those of opioids. At the same time, it causes far fewer undesirable reactions," said study author Roxana Damiescu of Johannes Gutenberg University in a press release.
An investigation of the genes affected by aniquinazolin B revealed that it works via different pathways compared to opioids. The researchers wrote that the compound should be further tested.
Sources: Science Daily, ChemMedChem